Tricyclic oxazolidinone antibiotic compounds

ABSTRACT

The present invention relates to antibacterial compounds of formula (I) wherein “----” is a bond or is absent, V is CH, CR 6  or N; R 0  is H or, if “----” is a bond, may also be alkoxy; R 1  is cyano, alkyl, or ethynyl; U is CH or N when “----” is a bond, or, if “----” is absent, U is CH 2 , NH or NH 9 ; R 2  is H, alkylcarbonyl or CH 2 —R 3 ; R 3  is H, alkyl or hydroxyalkyl; R 4  is H or, if n is not 0 and R 5  is H, may also be OH; R 5  is H, alkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, carboxy or alkoxycarbonyl; R 6  is hydroxyalkyl, carboxy, alkoxycarbonyl or —(CH 2 ) q —NR 7 R 8 , q being 1, 2 or 3 and each of R 7  and R 8  independently being H or alkyl or R 7  and R 8  forming with the N atom bearing them a ring; R 9  is alkyl or hydroxyalkyl; A is —(CH 2 ) p —, —CH 2 CH 2 CH(OH)— or —COCH 2 CH(OH)—; G is substituted phenyl or G 1  or G 2 , wherein Q is O or S and X is CH or N; and Y 1 , Y 2  and Y 3  may each be CH or N; and n is 0 when A is —CH 2 CH 2 CH(OH)— or —COCH 2 CH(OH)—, and n is 0, 1 or 2 when A is —(CH 2 ) p —, p being 1, 2, 3 or 4, with the proviso that the sum of n and p is then 2, 3 or 4; and to salts of such compounds.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No.13/123,218, filed Apr. 7, 2011, now patented as U.S. Pat. No. 8,618,092,which is the national phase application of PCT/IB2009/054357, filed Oct.6, 2009, which claims the benefit of PCT/IB2008/054109, filed Oct. 7,2008, PCT/IB2009/051059, filed Mar. 13, 2009, and PCT/IB2009/052843,filed Jun. 30, 2009, the contents of each are hereby incorporated byreference in their entirety.

FIELD OF THE INVENTION

The present invention concerns tricyclic oxazolidinone antibioticcompounds, a pharmaceutical antibacterial composition containing themand the use of these compounds in the manufacture of a medicament forthe treatment of infections (e.g. bacterial infections). These compoundsare useful antimicrobial agents effective against a variety of human andveterinary pathogens including among others Gram-positive andGram-negative aerobic and anaerobic bacteria and mycobacteria.

BACKGROUND OF THE INVENTION

The intensive use of antibiotics has exerted a selective evolutionarypressure on microorganisms to produce genetically based resistancemechanisms. Modern medicine and socio-economic behaviour exacerbate theproblem of resistance development by creating slow growth situations forpathogenic microbes, e.g. in artificial joints, and by supportinglong-term host reservoirs, e.g. in immuno-compromised patients.

BRIEF SUMMARY OF THE INVENTION

In hospital settings, an increasing number of strains of Staphylococcusaureus, Streptococcus pneumoniae, Enterococcus spp., and Pseudomonasaeruginosa, major sources of infections, are becoming multi-drugresistant and therefore difficult if not impossible to treat:

-   -   S. aureus is resistant to β-lactams, quinolones and now even to        vancomycin;    -   S. pneumoniae is becoming resistant to penicillin or quinolone        antibiotics and even to new macrolides;    -   Enteroccocci are quinolone and vancomycin resistant and β-lactam        antibiotics are inefficacious against these strains;    -   Enterobacteriacea are cephalosporin and quinolone resistant;    -   P. aeruginosa are β-lactam and quinolone resistant.

Furthermore, the incidence of multi-drug-resistant Gram-negative strainssuch as Enterobacteriacae and Pseudomonas aeruginosa, is steadilyincreasing and new emerging organisms like Acinetobacter spp. orClostridium difficile, which have been selected during therapy with thecurrently used antibiotics, are becoming a real problem in hospitalsettings. Therefore, there is a high medical need for new antibacterialagents which overcome multidrug-resistant Gram-negative bacilli such asA. baumannii, ESBL-producing E. coli and Klebsiella species andPseudomonas aeruginosa (Clinical Infectious Diseases (2006), 42,657-68).

In addition, microorganisms that are causing persistent infections areincreasingly being recognized as causative agents or cofactors of severechronic diseases like peptic ulcers or heart diseases.

Azatricyclic antibiotic compounds have already been described in WO2007/071936 and WO 2007/122258 (disclosing3-oxo-1,2-dihydro-3H-2a,6-diaza-acenaphthyl ene-1-methyl derivatives),WO 2007/081597 (disclosing4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-1-methyl derivatives),WO 2007/115947 (disclosing3-oxo-5,6-dihydro-3H-pyrrolo[1,2,3-de]quinoxaline-6-methyl derivatives)and WO 2008/003690 (disclosing notably1-(7-oxo-5,6,9a,9b-tetrahydro-4H,7H-1,6a-diaza-phenalen-5-yl)-piperidine-4-yland1-(5-oxo-2,3,7a,10b-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinolin-2-yl)-piperidine-4-ylderivatives). More recently, further azatricyclic antibiotics have beendescribed in WO 2008/120003, WO 2008/128942, WO 2008/128953, WO2008/128962, WO 2009/000745 and WO 2009/087153 (all filed before, butpublished after the earliest priority date(s) of the presentapplication).

Quinoline, naphthyridine or quinoxaline spirooxazolidinone antibioticcompounds have already been described in WO 2008/026172. More recently,other antibiotic compounds comprising an oxazolidinone motif have beendisclosed in WO 2008/126024, WO 2008/126034, WO 2009/077989 and WO2009/104159 (all filed before, but published after the earliest prioritydate(s) of the present application).

Moreover, azatricyclic antibiotics comprising an oxazolidinone motifhave been described in WO 2009/104147 (the priority or filing dates ofwhich are earlier than some of or all those of the present application,while the publication took place after the priority dates of the presentapplication).

The Applicants have now found a new family of tricyclic antibioticcompounds corresponding to the formula I described hereafter.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

Various embodiments of the invention are presented hereafter:

i) The invention firstly relates to compounds of formula I

wherein“-----” is a bond or is absent;R⁰ represents H or, in the case “-----” is a bond, may also represent(C₁-C₃)alkoxy (in particular methoxy);R¹ represents H, halogen (notably F, Cl or Br), cyano, (C₁-C₃)alkyl(notably methyl) or ethynyl;U represents CH or N when “-----” is a bond, or, in case “----” isabsent, U represents CH₂, NH or NR⁹;V represents CH, CR⁶ or N;R² represents H, (C₁-C₃)alkylcarbonyl or a group of the formula —CH₂—R³;R³ represents H, (C₁-C₃)alkyl or (C₁-C₃)hydroxyalkyl;R⁴ represents H or, in the cases wherein n is not 0 and R⁵ is H, mayalso represent OH;R⁵ represents H, (C₁-C₃)alkyl (notably methyl), (C₁-C₃)hydroxyalkyl(notably hydroxymethyl), (C₁-C₃)aminoalkyl (notably amino methyl),(C₁-C₃)alkoxy(C₁-C₃)alkyl (notably methoxymethyl), carboxy or(C₁-C₃)alkoxycarbonyl (notably methoxycarbonyl);R⁶ represents (C₁-C₃)hydroxyalkyl (notably hydroxymethyl), carboxy,(C₁-C₃)alkoxycarbonyl or a group —(CH₂)_(q)—NR⁷R⁸ wherein q is 1, 2 or 3and each of R⁷ and R⁸ independently represents H or (C₁-C₃)alkyl or R⁷and R⁸ form together with the nitrogen atom bearing them a pyrrolidinyl,piperidinyl, morpholinyl or thiomorpholinyl ring;R⁹ represents (C₁-C₃)alkyl (notably methyl), 2-hydroxy-ethyl,2-hydroxy-propyl or 3-hydroxy-propyl;A represents —(CH₂)_(p)—, —CH₂CH₂CH(OH)— or —COCH₂CH(OH)—;G represents a phenyl group which is substituted once or twice in themeta and/or para position(s) by substituents selected independently from(C₁-C₄)alkyl, (C₁-C₃)alkoxy and a halogen (notably F), whereby a(C₁-C₃)alkoxy substituent is preferably a straight chain (C₁-C₃)alkoxyand in para position, or G is a group having one of the formulae G¹ andG² below

whereinQ is O or S and X is CH or N; andY¹, Y² and Y³ each represent CH, or Y¹ and Y³ each represent CH and Y²represents N, or Y¹ represents N, Y² represents CH or N and Y³represents CH, or Y¹ and Y² each represent CH and Y³ represents N; andn is 0 when A represents —CH₂CH₂CH(OH)— or —COCH₂CH(OH)—, and n is 0, 1or 2 when A represents (CH₂)_(p), p being 1, 2, 3 or 4, with the provisothat the sum of n and p is then 2, 3 or 4 (i.e. when n is 0, p is not 1,when n is 1, p is not 4 and when n is 2, p is neither 3 nor 4);and to salts (in particular pharmaceutically acceptable salts) ofcompounds of formula I.

The following paragraphs provide definitions of the various chemicalmoieties for the compounds according to the invention and are intendedto apply uniformly throughout the specification and claims, unless anotherwise expressly set out definition provides a broader or narrowerdefinition:

-   -   The term “alkyl”, used alone or in combination, refers to a        straight or branched chain alkyl group containing from one to        four carbon atoms. The term “(C₁-C_(x))alkyl” (x being an        integer) refers to a straight or branched chain alkyl group        containing 1 to x carbon atoms. For example, a (C₁-C₄)alkyl        group contains from one to four carbon atoms. Representative        examples of alkyl groups include methyl, ethyl, propyl,        iso-propyl, n-butyl, iso-butyl, sec-butyl and tert-butyl.        Preferred are methyl and ethyl. Most preferred is methyl.    -   The term “alkoxy”, used alone or in combination, refers to a        straight or branched chain alkoxy group containing from one to        four carbon atoms. The term “(C_(x)-C_(y))alkoxy” (x and y each        being an integer) refers to an alkoxy group as defined before        containing x to y carbon atoms. For example, a (C₁-C₃)alkoxy        group contains from one to three carbon atoms. Representative        examples of alkoxy groups include methoxy, ethoxy, n-propoxy and        iso-propoxy. Preferred are methoxy and ethoxy.    -   The term “hydroxyalkyl” refers to a straight or branched chain        alkyl group containing from one to four carbon atoms wherein one        of the hydrogen atoms has been replaced by a hydroxy group. The        term “(C₁-C_(x))hydroxyalkyl” (x being an integer) refers to an        hydroxyalkyl group wherein the alkyl group contains 1 to x        carbon atoms. Representative examples of (C₁-C₃)hydroxyalkyl        groups include, but are not limited to, hydroxymethyl,        2-hydroxy-ethyl, 1-hydroxy-ethyl and 2-hydroxy-propyl. Preferred        (C₁-C₃)hydroxyalkyl groups are hydroxymethyl and        2-hydroxy-propyl. The most preferred (C₁-C₃)hydroxyalkyl group        is hydroxymethyl.    -   The term “aminoalkyl” refers to a straight or branched chain        alkyl group containing from one to four carbon atoms wherein one        of the hydrogen atoms has been replaced by an amino group. The        term “(C₁-C_(x))aminoalkyl” (x being an integer) refers to an        aminoalkyl group wherein the alkyl group contains 1 to x carbon        atoms. Representative examples of (C₁-C₃)aminoalkyl groups        include, but are not limited to, aminomethyl, 2-amino-ethyl,        1-amino-ethyl and 2-amino-propyl. Preferred (C₁-C₃)aminoalkyl        groups are aminomethyl and 2-amino-propyl. The most preferred        (C₁-C₃)aminoalkyl group is aminomethyl.    -   The term “alkoxyalkyl” refers to an alkoxyalkyl group wherein        the alkoxy group is a (C₁-C₄)alkoxy group and the alkyl group is        a (C₁-C₄)alkyl group. The term “(C₁-C_(x))alkoxy(C₁-C_(y))alkyl”        (x and y being each independently an integer) refers to an        alkoxyalkyl group wherein the alkoxy group contains 1 to x        carbon atoms and the alkyl group contains 1 to y carbon atoms.        Representative examples of (C₁-C₃)alkoxy(C₁-C₃)alkyl groups        include, but are not limited to, methoxymethyl and ethoxymethyl.        The most preferred (C₁-C₃)alkoxy(C₁-C₃)alkyl group is        methoxymethyl.    -   The term “alkylcarbonyl” refers to an alkylcarbonyl group        wherein the alkyl is a straight or branched chain alkyl group        containing from one to four carbon atoms. The term        “(C₁-C_(x))alkylcarbonyl” (x being an integer) refers to an        alkylcarbonyl group wherein the alkyl is a straight or branched        chain alkyl group containing 1 to x carbon atoms. Representative        examples of (C₁-C₃)alkylcarbonyl groups include acetyl,        ethylcarbonyl, 1-propyl-carbonyl and 2-propyl-carbonyl.        Preferred (C₁-C₃)alkylcarbonyl groups are acetyl and        ethylcarbonyl. The most preferred (C₁-C₃)alkylcarbonyl group is        acetyl.    -   The term “alkoxycarbonyl” refers to an alkoxycarbonyl group        wherein the alkoxy group is a straight or branched chain alkoxy        group containing from one to four carbon atoms. The term        “(C₁-C_(x))alkoxycarbonyl” (x being an integer) refers to an        alkoxycarbonyl group wherein the alkoxy is a straight or        branched chain alkoxy group containing 1 to x carbon atoms.        Representative examples of (C₁-C₃)alkoxycarbonyl groups include        methoxycarbonyl, ethoxycarbonyl, 1-propoxy-carbonyl and        2-propoxy-carbonyl. Preferred (C₁-C₃)alkylcarbonyl groups are        methoxycarbonyl and ethoxycarbonyl. The most preferred        (C₁-C₃)alkylcarbonyl group is ethoxycarbonyl.    -   The term “halogen” refers to fluorine, chlorine, bromine or        iodine, and preferably to fluorine or chlorine.    -   When in the formula

-   -   A represents the radical —CH₂CH₂CH(OH)—, this means specifically        that the CH₂ part of said radical is attached to the        neighbouring nitrogen while the CH(OH) part of said radical is        attached to the oxazolidinone ring.    -   This is applicable mutatis mutandis to all radicals that make A        radicals (e.g. to the radicals A′ mentioned in the preparation        methods). As a further example, in the substructure A, if it is        stated that A represents —COCH₂CH(OH)—, it is thereby meant that        the CO group of said radical is attached to the neighbouring        nitrogen while the CH(OH) part of said radical is attached to        the oxazolidinone ring. In other words, the left part of a        radical is always attached to the right part of the radical that        is next to the left.

In this text, a bond interrupted by a wavy line shows a point ofattachment of the radical drawn to the rest of the molecule. Forexample, the radical drawn below

is the 3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl group.

The compounds of formula I according to this invention may contain oneor more stereogenic or asymmetric centers, such as one or moreasymmetric carbon atoms. The compounds of formula I may thus be presentas mixtures of stereoisomers or, preferably, as pure stereoisomers.Mixtures of stereoisomers may be separated in a manner known to a personskilled in the art.

Whenever the absolute stereochemistry indication “(R)” or “(S)” isomitted in the name of a compound although there is a correspondingasymmetric carbon atom, it is meant thereby that this compound namerefers to either the (R)-configured compound or the (S)-configuredcompound.

The relative configuration of stereoisomers having two asymmetriccenters is indicated in this text by using the wording (R*,R*) to referto either the (R,R)-configured stereomer or the (S,S)-configuredstereomer and the wording (R*,S*) to refer to either the(R,S)-configured stereomer or the (S,R)-configured stereomer. Thus, forexample,(1R*,2R*)-4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylicacid methyl ester refers to either(1R,2R)-4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylicacid methyl ester or(1S,2S)-4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylicacid methyl ester.

The present invention also includes isotopically labelled, especially ²H(deuterium) labelled compounds of formula I, which compounds areidentical to the compounds of formula I except that one or more atomshave each been replaced by an atom having the same atomic number but anatomic mass different from the atomic mass usually found in nature.Isotopically labelled, especially ²H (deuterium) labelled compounds offormula I and salts thereof are within the scope of the presentinvention. Substitution of hydrogen with the heavier isotope ²H(deuterium) may lead to greater metabolic stability, resulting e.g. inincreased in-vivo half-life or reduced dosage requirements, or may leadto reduced inhibition of cytochrome P450 enzymes, resulting e.g. in animproved safety profile. In one variant of the invention, the compoundsof formula I are not isotopically labelled, or they are labelled onlywith one or more deuterium atoms. In a sub-variant, the compounds offormula I are not isotopically labelled at all. Isotopically labelledcompounds of formula I may be prepared in analogy to the methodsdescribed hereinafter, but using the appropriate isotopic variation ofsuitable reagents or starting materials.

The term “pharmaceutically acceptable salts” refers to non-toxic,inorganic or organic acid and/or base addition salts. Reference can bemade to “Salt selection for basic drugs”, Int. J. Pharm. (1986), 33,201-217.

Besides, the term “room temperature” as used herein refers to atemperature of 25° C.

Unless used regarding temperatures, the term “about” placed before anumerical value “X” refers in the current application to an intervalextending from X minus 10% of X to X plus 10% of X, and preferably to aninterval extending from X minus 5% of X to X plus 5% of X. In theparticular case of temperatures, the term “about” placed before atemperature “Y” refers in the current application to an intervalextending from the temperature Y minus 10° C. to Y plus 10° C., andpreferably to an interval extending from Y minus 5° C. to Y plus 5° C.

ii) The invention relates notably to compounds of formula I according toembodiment i) that are also compounds of formula I_(P3)

wherein“-----” is a bond or is absent;R⁰ represents H or, in the case “-----” is a bond, may also represent(C₁-C₃)alkoxy (in particular methoxy);R¹ represents H, halogen (notably F or Br), cyano or (C₁-C₃)alkyl(notably methyl);U represents CH or N when “-----” is a bond, or, in case “----” isabsent, U represents CH₂ or NH;V represents CH, CR⁶ or N;R² represents H, (C₁-C₃)alkylcarbonyl or a group of the formula —CH₂—R³;R³ represents H, (C₁-C₃)alkyl or (C₁-C₃)hydroxyalkyl;R⁴ represents H or, in the cases wherein n is not 0 and R⁵ is H, mayalso represent OH;R⁵ represents H, (C₁-C₃)alkyl (notably methyl), (C₁-C₃)hydroxyalkyl(notably hydroxymethyl), (C₁-C₃)alkoxy(C₁-C₃)alkyl (notablymethoxymethyl) or (C₁-C₃)alkoxycarbonyl (notably methoxycarbonyl);R⁶ represents (C₁-C₃)hydroxyalkyl (notably hydroxymethyl), carboxy,(C₁-C₃)alkoxycarbonyl or a group —(CH₂)_(q)—NR⁷R⁸ wherein q is 1, 2 or 3and each of R⁷ and R⁸ independently represents H or (C₁-C₃)alkyl or R⁷and R⁸ form together with the nitrogen atom bearing them a pyrrolidinyl,piperidinyl, morpholinyl or thiomorpholinyl ring;A represents —(CH₂)_(p)—, —CH₂CH₂CH(OH)— or —COCH₂CH(OH)—;G represents a phenyl group which is substituted once or twice in themeta and/or para position(s) by substituents selected independently from(C₁-C₄)alkyl, (C₁-C₃)alkoxy and a halogen (notably F), whereby a(C₁-C₃)alkoxy substituent is preferably a straight chain (C₁-C₃)alkoxyand in para position, or G is a group having one of the formulae G¹ andG² below

whereinQ is O or S and X is CH or N; andY¹, Y² and Y³ each represent CH, or Y¹ and Y³ each represent CH and Y²represents N, orY¹ represents N, Y² represents CH or N and Y³ represents CH, or Y¹ andY² each represent CH and Y³ represents N; andn is 0 when A represents —CH₂CH₂CH(OH)— or —COCH₂CH(OH)—, and n is 0, 1or 2 when A represents (CH₂)_(p), p being 1, 2, 3 or 4, with the provisothat the sum of n and p is then 2, 3 or 4 (i.e. when n is 0, p is not 1,when n is 1, p is not 4 and when n is 2, p is neither 3 nor 4);and to salts (in particular pharmaceutically acceptable salts) ofcompounds of formula I_(P3).

iii) The invention furthermore relates notably to compounds of formula Iaccording to embodiment i) or ii) that are also compounds of formulaI_(P2)

wherein“-----” is a bond or is absent;R⁰ represents H or, in the case “-----” is a bond, may also represent(C₁-C₃)alkoxy (in particular methoxy);R¹ represents H or halogen (notably F);U represents CH or N when “-----” is a bond, or, in case “----” isabsent, U represents CH₂ or NH;V represents CH or N;R² represents H or a group of the formula —CH₂—R³, R³ being hydrogen,(C₁-C₃)alkyl or (C₁-C₃)hydroxyalkyl;A represents —(CH₂)_(p)—, —CH₂CH₂CH(OH)— or —COCH₂CH(OH)—;G represents a phenyl group which is substituted once or twice in themeta and/or para position(s) by substituents selected independently from(C₁-C₄)alkyl, (C₁-C₃)alkoxy and a halogen (notably F), whereby a(C₁-C₃)alkoxy substituent is preferably a straight chain (C₁-C₃)alkoxyand in para position, or G is a group having one of the formulae G¹ andG² below

whereinQ is O or S and X is CH or N; andY¹, Y² and Y³ each represent CH, or Y¹ and Y³ each represent CH and Y²represents N, or Y¹ represents N, Y² represents CH or N and Y³represents CH, or Y¹ and Y² each represent CH and Y³ represents N; andn is 0 when A represents —CH₂CH₂CH(OH)— or —COCH₂CH(OH)—, and n is 0, 1or 2 when A represents (CH₂)_(p), p being 1, 2, 3 or 4, with the provisothat the sum of n and p is then 2, 3 or 4 (i.e. when n is 0, p is not 1,when n is 1, p is not 4 and when n is 2, p is neither 3 nor 4);and to salts (in particular pharmaceutically acceptable salts) ofcompounds of formula I_(P2).

iv) The invention yet relates to compounds of formula I as defined inembodiment i), ii) or iii) that are also compounds of formula I_(P1)

wherein“-----” is a bond or is absent;R¹ represents H or halogen (notably F);V represents CH or N;U represents CH or N, or, in case “----” is absent, U represents CH₂ orNH;G represents a phenyl group which is substituted once or twice in themeta and/or para position(s) by substituents selected independently from(C₁-C₄)alkyl, (C₁-C₃)alkoxy and a halogen (notably F), whereby a(C₁-C₃)alkoxy substituent is preferably a straight chain (C₁-C₃)alkoxyand in para position, or G is a group having one of the formulae G¹ andG² below

whereinQ is O or S and X is CH or N; andY¹, Y² and Y³ each represent CH, or Y¹ and Y³ each represent CH and Y²represents N, or Y¹ represents N, Y² represents CH or N and Y³represents CH, or Y¹ and Y² each represent CH and Y³ represents N; andn is 0, 1 or 2 and p is 1, 2 or 3, with the proviso that the sum of nand p is either 2 or 3 (i.e. when n is 0, p is 2 or 3, when n is 1, p is1 or 2 and when n is 2, p is 1);and to salts (in particular pharmaceutically acceptable salts) ofcompounds of formula I_(P).

v) In particular, the invention relates to compounds of formula I asdefined in embodiment i) that are also compounds of formula I_(CE)

wherein“-----” is a bond, V represents CH and U represents CH or N, or “-----”is a bond, V represents CR⁶ and U represents CH, or also “-----” is abond, V represents N and U represents CH, or“-----” is absent, V represents CH and U represents CH₂, NH or NR⁹;

-   R⁰ represents H or, in the case “----” is a bond, may also represent    (C₁-C₃)alkoxy (in particular methoxy);    R¹ represents H, halogen (notably F, Cl or Br), cyano, (C₁-C₃)alkyl    (notably methyl) or ethynyl;    V represents CH, CR⁶ or N;    R² represents H, acetyl or a group of the formula —CH₂—R³;    R³ represents hydrogen, (C₁-C₃)alkyl or (C₁-C₃)hydroxyalkyl;    R⁴ represents H or, in the cases wherein n is not 0 and R⁵ is H, may    also represent OH;    R⁵ represents H, (C₁-C₃)alkyl (notably methyl), (C₁-C₃)hydroxyalkyl    (notably hydroxymethyl), (C₁-C₃)amino alkyl (notably amino methyl),    (C₁-C₃)alkoxy(C₁-C₃)alkyl (notably methoxymethyl), carboxy or    (C₁-C₃)alkoxycarbonyl (notably methoxycarbonyl);    R⁶ represents (C₁-C₃)hydroxyalkyl (notably hydroxymethyl), carboxy,    (C₁-C₃)alkoxycarbonyl or a group —(CH₂)_(q)—NR⁷R⁸ wherein q is 1, 2    or 3 (notably 1) and each of R⁷ and R⁸ independently represents H or    (C₁-C₃)alkyl or R⁷ and R⁸ form together with the nitrogen atom    bearing them a pyrrolidinyl or piperidinyl ring (notably a    pyrrolidinyl ring);    R⁹ represents (C₁-C₃)alkyl (notably methyl), 2-hydroxy-ethyl,    2-hydroxy-propyl or 3-hydroxy-propyl;    A represents —(CH₂)_(p)—, —CH₂CH₂CH(OH)— or —COCH₂CH(OH)—;    G represents a phenyl group which is substituted once or twice in    the meta and/or para position(s) by substituents selected    independently from (C₁-C₄)alkyl, (C₁-C₃)alkoxy and a halogen    (notably F), whereby a (C₁-C₃)alkoxy substituent is preferably a    straight chain (C₁-C₃)alkoxy and in para position, or G is a group    having one of the formulae G¹ and G²′ below

whereinQ is O or S and X is CH or N; andeach of Y¹ and Y³ represents CH, or one of Y¹ and Y³ represents N andthe other represents CH; andn is 0 when A represents —CH₂CH₂CH(OH)— or —COCH₂CH(OH)—, and n is 0, 1or 2 when A represents (CH₂)_(p), p being 1, 2, 3 or 4, with the provisothat the sum of n and p is then 2, 3 or 4 (i.e. when n is 0, p is not 1,when n is 1, p is not 4 and when n is 2, p is neither 3 nor 4);and to salts (in particular pharmaceutically acceptable salts) ofcompounds of formula I_(CE).

vi) Also in particular, the invention relates to compounds of formula Ias defined in embodiment i), ii) or v) that are also compounds offormula I_(CEP3)

wherein“-----” is a bond, V represents CH and U represents CH or N, or “-----”is a bond, V represents CR⁶ and U represents CH, or also “-----” is abond, V represents N and U represents CH, or“-----” is absent, V represents CH and U represents CH₂ or NH;R⁰ represents H or, in the case “-----” is a bond, may also represent(C₁-C₃)alkoxy (in particular methoxy);R¹ represents H, halogen (notably F or Br), cyano or (C₁-C₃)alkyl(notably methyl);V represents CH, CR⁶ or N;R² represents H, acetyl or a group of the formula —CH₂—R³;R³ represents hydrogen, (C₁-C₃)alkyl or (C₁-C₃)hydroxyalkyl;R⁴ represents H or, in the cases wherein n is not 0 and R⁵ is H, mayalso represent OH;R⁵ represents H, (C₁-C₃)alkyl (notably methyl), (C₁-C₃)hydroxyalkyl(notably hydroxymethyl), (C₁-C₃)alkoxy(C₁-C₃)alkyl (notablymethoxymethyl) or (C₁-C₃)alkoxycarbonyl (notably methoxycarbonyl);R⁶ represents (C₁-C₃)hydroxyalkyl (notably hydroxymethyl), carboxy,(C₁-C₃)alkoxycarbonyl or a group —(CH₂)_(q)—NR⁷R⁸ wherein q is 1, 2 or 3(notably 1) and each of R⁷ and R⁸ independently represents H or(C₁-C₃)alkyl or R⁷ and R⁸ form together with the nitrogen atom bearingthem a pyrrolidinyl or piperidinyl ring (notably a pyrrolidinyl ring);A represents —(CH₂)_(p)—, —CH₂CH₂CH(OH)— or —COCH₂CH(OH)—;G represents a phenyl group which is substituted once or twice in themeta and/or para position(s) by substituents selected independently from(C₁-C₄)alkyl, (C₁-C₃)alkoxy and a halogen (notably F), whereby a(C₁-C₃)alkoxy substituent is preferably a straight chain (C₁-C₃)alkoxyand in para position, or G is a group having one of the formulae G¹ andG²′ below

whereinQ is O or S and X is CH or N; andeach of Y¹ and Y³ represents CH, or one of Y¹ and Y³ represents N andthe other represents CH; andn is 0 when A represents —CH₂CH₂CH(OH)— or —COCH₂CH(OH)—, and n is 0, 1or 2 when A represents (CH₂)_(p), p being 1, 2, 3 or 4, with the provisothat the sum of n and p is then 2, 3 or 4 (i.e. when n is 0, p is not 1,when n is 1, p is not 4 and when n is 2, p is neither 3 nor 4);and to salts (in particular pharmaceutically acceptable salts) ofcompounds of formula I_(CE).

vii) The invention furthermore relates to compounds of formula I asdefined in embodiment i), ii), iii), v) or vi) that are also compoundsof formula I_(CEP2)

wherein“-----” is a bond, V represents CH and U represents CH or N or Vrepresents N and U represents CH, or “-----” is absent, V represents CHand U represents CH₂ or NH;R⁰ represents H or, in the case “-----” is a bond, may also represent(C₁-C₃)alkoxy (in particular methoxy);R¹ represents H or halogen (notably F);R² represents H or a group of the formula —CH₂—R³, R³ being(C₁-C₃)hydroxyalkyl;A represents —(CH₂)_(p)—, —CH₂CH₂CH(OH)— or —COCH₂CH(OH)—;G represents a phenyl group which is substituted once in a meta positionand once in the para position by substituents selected independentlyfrom (C₁-C₄)alkyl and a halogen (notably F), G represents a phenyl groupwhich is substituted in the para position by a substituent selected from(C₁-C₄)alkyl and (C₁-C₃)alkoxy, or also G is a group having one of theformulae G¹ and G²′ below

whereinX represents CH or N and Q represents O or S;each of Y¹ and Y³ represents CH, or one of Y¹ and Y³ represents N andthe other represents CH;n is 0 when A represents —CH₂CH₂CH(OH)— or —COCH₂CH(OH)—, and n is 0, 1or 2 when A represents (CH₂)_(p), p being 1, 2, 3 or 4, with theprovisos that when n is 0, p is 2 or 3, when n is 1, p is 1, 2 or 3 andwhen n is 2, p is 1;and to salts (in particular pharmaceutically acceptable salts) ofcompounds of formula I_(CEP2).

viii) The invention yet relates to compounds of formula I as defined inone of embodiments i) to vii) that are also compounds of formulaI_(CEP1)

whereinR¹ represents H or halogen (notably F);“-----” is a bond, V represents CH and U represents CH or N or Vrepresents N and U represents CH, or “-----” is absent, V represents CHand U represents CH₂;G represents a phenyl group which is substituted once in a meta positionand once in the para position by substituents selected independentlyfrom (C₁-C₄)alkyl and a halogen (notably F), or G is a group having oneof the formulae G¹′ and G²′ below

wherein Q represents O or S;n is 0, 1 or 2 and p is 1, 2 or 3, with the proviso that the sum of nand p is either 2 or 3 (i.e. when n is 0, p is 2 or 3, when n is 1, p is1 or 2 and when n is 2, p is 1);and to salts (in particular pharmaceutically acceptable salts) ofcompounds of formula I_(CEP1).

ix) According to one main variant of this invention, the compounds offormula I as defined in one of embodiments i) to viii) above will besuch that R¹ represents halogen (notably F, Cl or Br, preferably F or Brand in particular F).

x) According to another main variant of this invention, the compounds offormula I as defined in one of embodiments i) to viii) above will besuch that R¹ represents H.

xi) According to a further main variant of this invention, the compoundsof formula I as defined in embodiment i), ii), v) or vi) above will besuch that R¹ represents (C₁-C₃)alkyl (notably methyl).

xii) According to yet a further main variant of this invention, thecompounds of formula I as defined in embodiment i) or v) above will besuch that R¹ represents ethynyl.

xiii) One main embodiment of this invention relates to the compounds offormula I as defined in one of embodiments i) to xii) above wherein Vrepresents CH (and notably to compounds of formula I as defined inembodiment iv) or viii) wherein V represents CH and R¹ representsfluorine).

xiv) Another main embodiment of this invention relates to the compoundsof formula I as defined in one of embodiments i) to xii) above wherein Vrepresents N (and notably to compounds of formula I as defined inembodiment iv) or viii) wherein V represents N and R¹ representsfluorine).

xv) A further main embodiment of this invention relates to the compoundsof formula I as defined in embodiment i), ii), v) or vi) above wherein Vrepresents CR⁶.

xvi) According to one sub-embodiment of embodiment xv) above, R⁶ willrepresent (C₁-C₃)hydroxyalkyl (notably hydroxymethyl).

xvii) According to another sub-embodiment of embodiment xv) above, R⁶will represent carboxy.

xviii) According to yet another sub-embodiment of embodiment xv) above,R⁶ will represent (C₁-C₃)alkoxycarbonyl (notably ethoxycarbonyl).

xix) According to a further sub-embodiment of embodiment xv) above, R⁶will represent a group —(CH₂)_(q)—NR⁷R⁸ wherein q is 1, 2 or 3 (inparticular 1) and each of R⁷ and R⁸ independently represents H or(C₁-C₃)alkyl or R⁷ and R⁸ form together with the nitrogen atom bearingthem a pyrrolidinyl, piperidinyl, morpholinyl or thiomorpholinyl ring,and in particular a pyrrolidinyl or piperidinyl ring (such a group—(CH₂)_(q)—NR⁷R⁸ being notably dimethylaminomethyl orpyrrolidin-1-ylmethyl).

xx) A further embodiment of this invention relates to the compounds offormula I as defined in one of embodiments i) to xix) above wherein“-----” is a bond; such embodiment thus notably relates to compounds offormula I as defined in embodiment iv) or viii) wherein “-----” is abond and:

-   -   R¹ represents fluorine, or    -   R¹ represents fluorine and V represents CH, or    -   R¹ represents fluorine and V represents N.

xxi) One sub-embodiment of embodiment xx) above relates to the compoundsof formula I as defined in embodiment xx) above wherein U represents CH(and notably to the compounds of formula I as defined in embodiment xiv)above wherein U represents CH and R⁰ represents H).

xxii) Another sub-embodiment of embodiment xx) above relates to thecompounds of formula I as defined in embodiment xx) above wherein Urepresents N.

xxiii) According to one variant of sub-embodiment xxii), the compoundsof formula I as defined in embodiment xxii) above will be such that R⁰represents H (and notably such that R⁰ represents H and V representsCH).

xxiv) According to the other variant of sub-embodiment xxii), thecompounds of formula I as defined in embodiment xxii) above will be suchthat R⁰ represents (C₁-C₃)alkoxy (and in particular methoxy); thisparticular variant relates notably to compounds of formula I as definedin one of embodiments i) to iii) or v) to vii) wherein R⁰ represents(C₁-C₃)alkoxy (and in particular methoxy) and:

-   -   R¹ represents halogen (and preferably F), or    -   R¹ represents H, or    -   R¹ represents halogen (and preferably F) and V represents CH, or    -   R¹ represents halogen (and preferably F) and V represents N, or    -   R¹ represents H and V represents CH, or    -   R¹ represents H and V represents N, or    -   V represents CH, or    -   V represents N.

xxv) Yet a further embodiment of this invention relates to the compoundsof formula I as defined in one of embodiments i) to xix) above wherein“-----” is absent and U represents CH₂ or NH (notably CH₂); suchembodiment thus notably to compounds of formula I as defined inembodiment iv) or viii) wherein “-----” is absent, U represents CH₂ and:

-   -   R¹ represents fluorine, or    -   R¹ represents fluorine and V represents CH, or    -   R¹ represents fluorine and V represents N, or    -   V represents CH, or    -   V represents N.

xxvi) One particular embodiment of this invention relates to thecompounds of formula I as defined in embodiment i), ii), v) or vi), oras defined in embodiment i), ii), v) or vi) taken together with any ofembodiments ix) to xxv), wherein R⁴ represents H.

xxvii) One sub-embodiment of embodiment xxvi) relates to compounds offormula I as defined in embodiment xxvi) wherein each of R⁴ and R⁵represents H.

xxviii) Another particular embodiment of this invention relates to thecompounds of formula I as defined in embodiment i), ii), v) or vi), oras defined in embodiment i), ii), v) or vi) taken together with any ofembodiments ix) to xxv), wherein n is 1 or 2, R⁴ represents OH and R⁵represents H.

xxix) Yet another particular embodiment of this invention relates to thecompounds of formula I as defined in embodiment i) or v), or as definedin embodiment i) or v) taken together with any of embodiments ix) toxxv), wherein R⁵ represents (C₁-C₃)alkyl (notably methyl),(C₁-C₃)hydroxyalkyl (notably hydroxymethyl), (C₁-C₃)aminoalkyl (notablyaminomethyl), (C₁-C₃)alkoxy(C₁-C₃)alkyl (notably methoxymethyl), carboxyor (C₁-C₃)alkoxycarbonyl (notably methoxycarbonyl).

xxx) In particular, the compounds of formula I as defined in embodimentxxix) will be compounds of formula I as defined in embodiment ii) orvi), or as defined in embodiment ii) or vi) taken together with any ofembodiments ix) to xxv), wherein R⁵ represents (C₁-C₃)alkyl (notablymethyl), (C₁-C₃)hydroxyalkyl (notably hydroxymethyl),(C₁-C₃)alkoxy(C₁-C₃)alkyl (notably methoxymethyl) or(C₁-C₃)alkoxycarbonyl (notably methoxycarbonyl).

xxxi) According to one variant of embodiment xxix) or xxx), R⁵ willrepresent (C₁-C₃)alkyl (notably methyl).

xxxii) According to another variant of embodiment xxix) or xxx), R⁵ willrepresent (C₁-C₃)hydroxyalkyl (notably hydroxymethyl or1-hydroxy-1-methyl-ethyl and in particular hydroxymethyl).

xxxiii) According to yet another variant of embodiment xxix) or xxx), R⁵will represent (C₁-C₃)alkoxy(C₁-C₃)alkyl (notably methoxymethyl).

xxxiv) According to a further variant of embodiment xxix), R⁵ willrepresent (C₁-C₃)alkoxycarbonyl (notably methoxycarbonyl).

xxxv) According to yet a further variant of embodiment xxix), R⁵ willrepresent (C₁-C₃)aminoalkyl (notably aminomethyl).

xxxvi) According to yet a further variant of embodiment xxix), R⁵ willrepresent carboxy.

xxxvii) According to one main variant of this invention, the compoundsof formula I as defined in one of embodiments i) to xxxvi) will be suchthat A represents —(CH₂)_(p)— (whereby in such case the compounds offormula I wherein n is 0 and p is 2 or 3, or n is 1 and p is 1, 2 or 3,or n is 2 and p is 1 will in a general manner be preferred).

xxxviii) According to one sub-embodiment of embodiment xxxvii), thecompounds of formula I as defined in embodiment xxxvii) will be suchthat the sum of n and p is 2.

xxxix) According to one variant of embodiment xxxviii), the compounds offormula I will be such that n is 0 and p is 2.

xl) According to another variant of embodiment xxxviii), the compoundsof formula I will be such that n is 1 and p is 1.

xli) According to another sub-embodiment of embodiment xxxvii), thecompounds of formula I as defined in embodiment xxxvii) will be suchthat the sum of n and p is 3 (and notably such that the sum of n and pis 3, each of R⁰, R⁴ and R⁵ represents H and G is a group of the formulaG¹ or G² as defined in embodiment i), ii) or iii)).

xlii) According to one variant of embodiment xli), the compounds offormula I will be such that n is 0 and p is 3.

xliii) The compounds of formula I as defined in embodiment xlii) willnotably be such that “-----” is a bond, each of R⁰, R⁴ and R⁵ representsH, R¹ represents H or F (in particular F), V represents CH, U representsCH or N and G is a group of the formula G¹ or G² as defined inembodiment i), ii) or iii) (and in particular a group of the formula G¹as defined in embodiment i), ii) or iii), notably such a group of theformula G¹ wherein X is CH and Q is S).

xliv) According to another variant of embodiment xli), the compounds offormula I will be such that n is 1 and p is 2.

xlv) The compounds of formula I as defined in embodiment xliv) willnotably be such that “-----” is a bond, each of R⁰, R⁴ and R⁵ representsH, R¹ represents H or F (in particular F), V represents CH, U representsCH or N and G is a group of the formula G¹ or G² as defined inembodiment i), ii) or iii) (and in particular a group of the formula G¹as defined in embodiment i), ii) or iii), notably such a group of theformula G¹ wherein X is CH and Q is S).

xlvi) According to yet another variant of embodiment xli), the compoundsof formula I will be such that n is 2 and p is 1.

xlvii) The compounds of formula I as defined in embodiment xlvi) willnotably be such that “-----” is a bond, each of R⁰, R⁴ and R⁵ representsH, R¹ represents H or F (in particular F), V represents CH, U representsCH or N and G is a group of the formula G¹ or G² as defined inembodiment i), ii) or iii) (and in particular a group of the formula G¹as defined in embodiment i), ii) or iii), notably such a group of theformula G¹ wherein X is CH and Q is S).

xlviii) According to another sub-embodiment of embodiment xxxvii), thecompounds of formula I as defined in embodiment xxxvii) will be suchthat the sum of n and p is 4.

il) According to one variant of embodiment xlviii), the compounds offormula I will be such that n is 0 and p is 4.

l) According to another variant of embodiment xlviii), the compounds offormula I will be such that n is 1 and p is 3.

li) According to yet another variant of embodiment xlviii), thecompounds of formula I will be such that n is 2 and p is 2.

lii) Another main variant of this invention relates to the compounds offormula I as defined in embodiment i), ii), iii), v), vi) or vii)wherein A represents —CH₂CH₂CH(OH)—, or to the compounds of formula I asdefined in embodiment i), ii), iii), v), vi) or vii) taken together withany of embodiments ix) to xxxvi) wherein A represents —CH₂CH₂CH(OH)—.

liii) Yet another main variant of this invention relates to thecompounds of formula I as defined in embodiment i), ii), iii), v), vi)or vii) wherein A represents —COCH₂CH(OH)—, or to the compounds offormula I as defined in embodiment i), ii), iii), v), vi) or vii) takentogether with any of embodiments vii) to xxxvi) wherein A represents—COCH₂CH(OH)—.

liv) A further embodiment of this invention relates to the compounds offormula I as defined in embodiment i), ii), iii), v), vi) or vii)wherein R² represents H, or to the compounds of formula I as defined inembodiment i), ii), iii), v), vi) or vii) taken together with any ofembodiments ix) to liii) wherein R² represents H.

lv) Yet a further embodiment of this invention relates to the compoundsof formula I as defined in embodiment i), ii), iii), v), vi) or vii)wherein R² represents a group of the formula —CH₂—R³, R³ being hydrogen,(C₁-C₃)alkyl or (C₁-C₃)hydroxyalkyl, or to the compounds of formula I asdefined in embodiment i), ii), iii), v), vi) or vii) taken together withany of embodiments ix) to liii) wherein R² represents a group of theformula —CH₂—R³, R³ being hydrogen, (C₁-C₃)alkyl or (C₁-C₃)hydroxyalkyl(and in particular to the compounds of formula I as defined inembodiment iii) or vii) wherein R² represents a group of the formula—CH₂—R³, R³ being (C₁-C₃)alkyl or (C₁-C₃)hydroxyalkyl, or to thecompounds of formula I as defined in embodiment iii) or vii) takentogether with any of embodiments ix), x), xiii), xiv), xx) to xxv) andxxxvii) to liii) wherein R² represents a group of the formula —CH₂—R³,R³ being (C₁-C₃)alkyl or (C₁-C₃)hydroxyalkyl).

lvi) According to one variant of embodiment lv), the compounds offormula I as defined in embodiment lv) will be such that R² represents agroup of the formula —CH₂—R³ wherein R³ is hydrogen or (C₁-C₃)alkyl.

lvii) According to another variant of embodiment lv), the compounds offormula I as defined in embodiment lv) will be such that R² represents agroup of the formula —CH₂—R³ wherein R³ is (C₁-C₃)hydroxyalkyl (inparticular such that R² represents a group 2-hydroxy-ethyl or3-hydroxy-propyl).

lviii) Yet a further embodiment of this invention relates to thecompounds of formula I as defined in embodiment i), ii), v) or vi)wherein R² represents (C₁-C₃)alkylcarbonyl (notably acetyl), or to thecompounds of formula I as defined in embodiment i), ii), v) or vi) takentogether with any of embodiments ix) to liii) wherein R² represents(C₁-C₃)alkylcarbonyl (notably acetyl).

lix) According to one particular embodiment of this invention, thecompounds of formula I as defined in embodiments i) to lviii) above willbe such that G represents a group of the formula G¹, or, in theembodiments referring to embodiment viii), the group G¹′.

lx) Preferably, the compounds of formula I as defined in embodiment lix)above will be such that X, if present, represents CH (that is, Grepresents 3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl or3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl); a particular sub-embodimentof this embodiment will relate to compounds of formula I as defined inembodiment iv) or viii) wherein G represents3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl or3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl and:

-   -   R¹ represents fluorine, or    -   V represents CH, or    -   V represents N, or    -   R¹ represents fluorine and V represents CH, or    -   R¹ represents fluorine and V represents N, or    -   R¹ represents fluorine and “-----” is a bond, or    -   R¹ represents fluorine, “-----” is a bond and V represents CH,    -   R¹ represents fluorine, “-----” is a bond and V represents N,    -   “-----” is absent and U represents CH₂, or    -   R¹ represents fluorine, “-----” is absent and U represents CH₂,        or    -   R¹ represents fluorine, V represents CH, “-----” is absent and U        represents CH₂, or    -   R¹ represents fluorine, V represents N, “-----” is absent and U        represents CH₂.

lxi) According to another particular embodiment of this invention, thecompounds of formula I as defined in embodiments i) to lviii) above willbe such that G represents a group of the formula G², or, in theembodiments referring to embodiment v), vi), vii) or viii), the groupG²′.

lxii) According to a variant of embodiment lxi), the compounds offormula I as defined in embodiment lxi) above will be such that eithereach of Y¹, Y² and Y³, if present, represents CH, or one of Y¹ and Y³,if present, represents N and Y² and the other of Y¹ and Y³, if present,each represent CH (that is, G represents2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl,2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-6-yl or2,3-dihydro-benzo[1,4]dioxin-6-yl).

lxiii) Preferably, the compounds of formula I as defined in embodimentlxii) above will be such that each of Y¹, Y² and Y³, if present,represents CH (that is, G represents 2,3-dihydro-benzo[1,4]dioxin-6-yl).

lxiv) According to yet another particular embodiment of this invention,the compounds of formula I as defined in embodiments i) to lviii) abovewill be such that G represents a phenyl group which is substituted onceor twice in the meta and/or para position(s) by substituents selectedindependently from (C₁-C₄)alkyl, (C₁-C₃)alkoxy and a halogen (notablyF), whereby a (C₁-C₃)alkoxy substituent, if present, is preferably astraight chain (C₁-C₃)alkoxy and in para position, or, in theembodiments referring to embodiment vii) or viii), such that Grepresents a phenyl group which is substituted once in a meta positionand once in the para position by substituents selected independentlyfrom (C₁-C₄)alkyl and a halogen (notably F).

lxv) Preferably, the compounds of formula I as defined in embodimentlxiv) above will be such that G represents a phenyl group which issubstituted once or twice in the meta and/or para position(s) bysubstituents selected independently from methyl, ethyl, methoxy, ethoxyand halogen (notably F), whereby a methoxy or ethoxy substituent, ifpresent, is in para position, or, in the embodiments referring toembodiment vii) or viii), such that G represents a phenyl group which issubstituted once in a meta position and once in the para position bysubstituents selected independently from methyl and fluorine.

lxvi) In particular, the compounds of formula I as defined in embodimentlxiv) or lxv) above will be such that G represents3-fluoro-4-methyl-phenyl.

lxvii) Yet a further embodiment of this invention relates to compoundsof formula I as defined in embodiment i), ii), v) or vi) wherein:

-   -   “-----” is a bond, V represents CH and U represents CH or N, or        “-----” is absent and U represents NH;    -   R⁰ represents H or, in the case “-----” is a bond, may also        represent (C₁-C₃)alkoxy (in particular methoxy);    -   R¹ represents H or halogen (notably H, F or Br, and in        particular H or F);    -   R² represents H;    -   each of R⁴ and R⁵ represents H;    -   n is 0;    -   A represents —(CH₂)_(p)—, p being 3;    -   G is a group having the formula G¹ below

-   -   wherein X is CH or N and Q is O or S;        and to salts (in particular pharmaceutically acceptable salts)        of such compounds.

lxviii) According to one sub-embodiment of embodiment lxvii), thecompounds of formula I as defined in embodiment lxiv) will be such that“-----” is a bond, V represents CH and U represents CH or N.

lxix) According to another sub-embodiment of embodiment lxvii), thecompounds of formula I as defined in embodiment lxiv) will be such that“-----” is absent and U represents NH.

lxx) Yet a further embodiment of this invention relates to compounds offormula I as defined in embodiment i), ii), v) or vi) wherein:

-   -   “-----” is a bond, V represents CH and U represents CH or N, or        “-----” is absent and U represents NH;    -   R⁰ represents H or, in the case “-----” is a bond, may also        represent (C₁-C₃)alkoxy (in particular methoxy);    -   R¹ represents H or halogen (notably F or Br, in particular F);    -   R² represents H;    -   R⁴ represents H;    -   R⁵ represents H, (C₁-C₃)alkyl (notably methyl),        (C₁-C₃)hydroxyalkyl (notably hydroxymethyl),        (C₁-C₃)alkoxy(C₁-C₃)alkyl (notably methoxymethyl) or        (C₁-C₃)alkoxycarbonyl (notably acetyl);    -   n is 0;    -   A represents —(CH₂)_(p)—, p being 3; and    -   G is a group having the formula G²′ below

-   -   wherein each of Y¹ and Y³ represents CH, or one of Y¹ and Y³        represents N and the other represents CH (and in particular        wherein each of Y¹ and Y³ represents CH);        and to salts (in particular pharmaceutically acceptable salts)        of such compounds.

lxxi) According to one sub-embodiment of embodiment lxx), the compoundsof formula I as defined in embodiment lxx) will be such that “-----” isa bond, V represents CH and U represents CH or N.

lxxii) According to another sub-embodiment of embodiment lxx), thecompounds of formula I as defined in embodiment lxx) will be such that“-----” is absent and U represents NH.

lxxiii) One main embodiment of this invention relates to the compoundsof formula I as defined in one of embodiments i) to xxvii) or xxix) toxxxvii), and in particular according to embodiment i) or v)), wherein nis 0 (and notably wherein n is 0, A represents (CH₂)_(p) and p is 2 or3).

lxxiv) Another main embodiment of this invention relates to thecompounds of formula I as defined in one of embodiments i) to xxvii) orxxix) to xxxvii), and in particular according to embodiment i) or v)),wherein n is 1 (and notably wherein n is 1, A represents (CH₂)_(p) and pis 1 or 2).

lxxv) Yet another main embodiment of this invention relates to thecompounds of formula I as defined in one of embodiments i) to xxvii) orxxix) to xxxvii), and in particular according to embodiment i) or v)),wherein n is 2 (and notably wherein n is 2, A represents (CH₂)_(p) and pis 1 or 2).

lxxvi) Yet a further embodiment of this invention relates to thecompounds of formula I as defined in embodiment i) or v) wherein:

-   -   “-----” is a bond and V represents CH and U represents CH or N        or V represents N and U represents CH;    -   R⁰ represents H;    -   R¹ represents H or fluorine (in particular fluorine);    -   R² represents H;    -   R⁴ represents H;    -   R⁵ represents H, methyl, hydroxymethyl or aminomethyl (and in        particular H);    -   n is 0 and A represents —(CH₂)_(p)— wherein p is 2, 3 or 4, or n        is 1 and A represents —(CH₂)_(p)— wherein p is 1, 2 or 3; and    -   G is a group having the formula G¹ below

-   -   wherein X is CH or N and Q is O or S;        and to salts (in particular pharmaceutically acceptable salts)        of such compounds.

lxxvii) Yet another embodiment of this invention relates to compounds offormula I as defined in embodiment i) or v) wherein:

-   -   “-----” is absent and U represents NH or NR⁹ wherein R⁹ is        methyl (and in particular NH);    -   R⁰ represents H;    -   R¹ represents H or fluorine (in particular fluorine);    -   R² represents H;    -   each of R⁴ and R⁵ represents H;    -   n is 0 and A represents —(CH₂)_(p)— wherein p is 2, 3 or 4, or n        is 1 and A represents —(CH₂)_(p)— wherein p is 1, 2 or 3; and    -   G is a group having the formula G¹ below

-   -   wherein X is CH or N and Q is O or S;        and to salts (in particular pharmaceutically acceptable salts)        of such compounds.

lxxviii) According to one particular variant of this invention, thecompounds of formula I as defined in embodiments i) to lxxvii) abovewill be such that their stereochemistry is as drawn below

or, in the particular case of compounds of formula I_(P2), such thattheir stereochemistry is as drawn below

or also, in the particular case of compounds of formula I_(P1), suchthat their stereochemistry is as drawn below

lxxix) According to one sub-variant of embodiment lxxviii), thecompounds of formula I as defined in embodiment lxxviii) will be suchthat their stereochemistry is as drawn below

or, in the particular case of compounds of formula I_(P2), such thattheir stereochemistry is as drawn below

or also, in the particular case of compounds of formula I_(P1), suchthat their stereochemistry is as drawn below

lxxx) According to the other sub-variant of embodiment lxxviii), thecompounds of formula I as defined in embodiment lxxviii) will be suchthat their stereochemistry is as drawn below

or, in the particular case of compounds of formula Ip₂, such that theirstereochemistry is as drawn below

or also, in the particular case of compounds of formula I_(P1), suchthat their stereochemistry is as drawn below

lxxxi) According to another particular variant of this invention, thecompounds of formula I as defined in embodiments i) to lxxvii) abovewill be such that their stereochemistry is as drawn below

or, in the particular case of compounds of formula I_(P2), such thattheir stereochemistry is as drawn below

or also, in the particular case of compounds of formula I_(P1), suchthat their stereochemistry is as drawn below

lxxxii) According to one sub-variant of embodiment lxxxi), the compoundsof formula I as defined in embodiment lxxxi) will be such that theirstereochemistry is as drawn below

or, in the particular case of compounds of formula I_(P2), such thattheir stereochemistry is as drawn below

or also, in the particular case of compounds of formula I_(P1), suchthat their stereochemistry is as drawn below

lxxxiii) According to the other sub-variant of embodiment lxxxi), thecompounds of formula I as defined in embodiment lxxxi) will be such thattheir stereochemistry is as drawn below

or, in the particular case of compounds of formula I_(P2), such thattheir stereochemistry is as drawn below

or also, in the particular case of compounds of formula I_(P1), suchthat their stereochemistry is as drawn below

lxxxiv) According to yet another particular variant of this invention,the compounds of formula I as defined in embodiments i) to lxxvii) abovewill be such that their stereochemistry is as drawn below

or, in the particular case of compounds of formula I_(P2), such thattheir stereochemistry is as drawn below

or also, in the particular case of compounds of formula I_(P1), suchthat their stereochemistry is as drawn below

lxxxv) According to yet another particular variant of this invention,the compounds of formula I as defined in embodiments i) to lxxvii) abovewill be such that their stereochemistry is as drawn below

or, in the particular case of compounds of formula I_(P2), such thattheir stereochemistry is as drawn below

or also, in the particular case of compounds of formula I_(P1), suchthat their stereochemistry is as drawn below

lxxxvi) Particularly preferred are the following compounds of formula Ias defined in one of embodiments i) to viii):

-   9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-({2-[3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   1-(2-{[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-ethyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-(2-{[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-(2-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-(2-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-(2-{[(R)-3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-{2-[2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (4R)-4-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   3-fluoro-4-(2-{[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   3-fluoro-4-(2-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (4R)-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (4R)-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   9-fluoro-1-(2-{[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-(2-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-(2-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   1-(2-{[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-ethyl)-9-fluoro-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-(2-{[(R)-3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   3-fluoro-4-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-({[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   1-({[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-({[(R)-3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;    as well as the salts (in particular the pharmaceutically acceptable    salts) thereof.

lxxxvii) A further object of this invention thus relates to thefollowing compounds of formula I as defined in one of embodiments i) toviii):

-   (1R)-9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S)-9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo    quinolin-4-one;-   (1R)-9-fluoro-1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S)-9-fluoro-1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R)-9-fluoro-1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S)-9-fluoro-1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R)-9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S)-9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R)-9-fluoro-1-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S)-9-fluoro-1-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R)-9-fluoro-1-({2-[(R)-3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R)-9-fluoro-1-({2-[(S)-3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S)-9-fluoro-1-({2-[(R)-3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S)-9-fluoro-1-({2-[(S)-3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R)-1-(2-{[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-ethyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S)-1-(2-{[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-ethyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R)-9-fluoro-1-(2-{[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S)-9-fluoro-1-(2-{[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R)-9-fluoro-1-(2-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S)-9-fluoro-1-(2-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R)-9-fluoro-1-(2-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S)-9-fluoro-1-(2-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R)-9-fluoro-1-(2-{[(R)-3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S)-9-fluoro-1-(2-{[(R)-3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R)-9-fluoro-1-{2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R)-9-fluoro-1-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S)-9-fluoro-1-{2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S)-9-fluoro-1-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (4R)-4-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (4R)-3-fluoro-4-(2-{[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (4S)-3-fluoro-4-(2-{[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (4R)-3-fluoro-4-(2-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (4S)-3-fluoro-4-(2-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (4R)-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (4R)-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (6R)-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (6S)-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (6R)-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (6S)-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (1R)-9-fluoro-1-(2-{[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S)-9-fluoro-1-(2-{[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R)-9-fluoro-1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S)-9-fluoro-1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R)-9-fluoro-1-(2-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S)-9-fluoro-1-(2-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R)-9-fluoro-1-(2-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S)-9-fluoro-1-(2-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R)-1-(2-{[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-ethyl)-9-fluoro-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S)-1-(2-{[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-ethyl)-9-fluoro-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R)-9-fluoro-1-(2-{[(R)-3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S)-9-fluoro-1-(2-{[(R)-3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (4R)-3-fluoro-4-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (4S)-3-fluoro-4-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (1R)-9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S)-9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R)-9-fluoro-1-({[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S)-9-fluoro-1-({[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R)-1-({[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S)-1-({[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R)-9-fluoro-1-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S)-9-fluoro-1-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R)-9-fluoro-1-({[(R)-3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S)-9-fluoro-1-({[(R)-3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;    as well as to the salts (in particular the pharmaceutically    acceptable salts) thereof.

lxxxviii) Further particularly preferred compounds of formula I asdefined in embodiment i), ii), iii), v), vi) or vii) are the followingcompounds:

-   4-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   1-({[(R)-3-(4-ethoxy-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-({[(R)-2-oxo-3-(4-propyl-phenyl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   1-({[(R)-3-(4-butyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-4-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   1-({2-[3-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   1-({2-[3-(2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-6-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   1-({2-[(R)-3-(4-ethoxy-phenyl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-({2-[(R)-2-oxo-3-(4-propyl-phenyl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   1-({2-[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-({2-[2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (S)-9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-({3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-({3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-6-{2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (S)-6-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   6-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (S)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (S)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   9-fluoro-1-{2-[(R)-2-oxo-3-(4-propyl-phenyl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   1-({2-[(S)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   1-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (R)-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (S)-7-fluoro-6-((2-hydroxy-ethyl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (S)-7-fluoro-6-((2-hydroxy-ethyl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   9-fluoro-1-(2-{(3-hydroxy-propyl)-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-(2-{(2-hydroxy-ethyl)-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (S)-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (S)-4-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-4-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (R)-4-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-7-fluoro-6-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (S)-7-fluoro-6-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   1-({[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   1-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   1-({3-[2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   3-fluoro-4-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-{2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-[((3-hydroxy-propyl)-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl}-amino)-methyl]-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-[((2-hydroxy-ethyl)-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl}-amino)-methyl]-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-((3-hydroxy-propyl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-((2-hydroxy-ethyl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   3-fluoro-4-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   3-fluoro-4-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   3-fluoro-4-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   3-fluoro-4-({[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   3-fluoro-4-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   3-fluoro-4-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (R)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (R)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   6-({[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   1-{2-[(S)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   N—((S)-9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-3-hydroxy-3-[2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propionamide;-   (R)-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   6-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (R)-7-fluoro-2-methoxy-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (R)-7-fluoro-2-methoxy-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   9-fluoro-1-{3-hydroxy-3-[2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-one;    as well as the salts (in particular the pharmaceutically acceptable    salts) thereof

lxxxix) A further object of this invention thus relates to the followingcompounds of formula I as defined in embodiment i), ii), iii), v), vi)or vii):

-   (R)-4-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-4-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (R)-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-1-({[(R)-3-(4-ethoxy-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-({[(R)-3-(4-ethoxy-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-({[(R)-2-oxo-3-(4-propyl-phenyl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-({[(R)-2-oxo-3-(4-propyl-phenyl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-1-({[(R)-3-(4-butyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-({[(R)-3-(4-butyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-4-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (R)-1-({2-[(R)-3-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-1-({2-[(S)-3-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-({2-[(R)-3-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-({2-[(S)-3-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-1-({2-[(R)-3-(2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-6-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-1-({2-[(S)-3-(2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-6-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-({2-[(R)-3-(2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-6-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-({2-[(S)-3-(2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-6-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-1-({2-[(R)-3-(4-ethoxy-phenyl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-({2-[(R)-3-(4-ethoxy-phenyl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-({2-[(R)-2-oxo-3-(4-propyl-phenyl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-({2-[(R)-2-oxo-3-(4-propyl-phenyl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-1-({2-[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-({2-[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (S)-9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-({3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-({3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-({3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-({3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-6-{2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (S)-6-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (R)-6-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (S)-6-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (S)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (S)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (R)-9-fluoro-1-{2-[(R)-2-oxo-3-(4-propyl-phenyl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-{2-[(R)-2-oxo-3-(4-propyl-phenyl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-1-({2-[(S)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-({2-[(S)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-1-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (R)-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (S)-7-fluoro-6-((2-hydroxy-ethyl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (S)-7-fluoro-6-((2-hydroxy-ethyl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (R)-9-fluoro-1-(2-{(3-hydroxy-propyl)-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-(2-{(3-hydroxy-propyl)-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-(2-{(2-hydroxy-ethyl)-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-(2-{(2-hydroxy-ethyl)-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (S)-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (S)-4-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-4-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (R)-4-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-7-fluoro-6-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (S)-7-fluoro-6-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (R)-1-({[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-({[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-1-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-1-({3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-1-({3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-({3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-({3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-3-fluoro-4-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-3-fluoro-4-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-{2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-[((3-hydroxy-propyl)-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl}-amino)-methyl]-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-[((3-hydroxy-propyl)-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl}-amino)-methyl]-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-[((2-hydroxy-ethyl)-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl}-amino)-methyl]-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-[((2-hydroxy-ethyl)-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl}-amino)-methyl]-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-((3-hydroxy-propyl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-((3-hydroxy-propyl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-((2-hydroxy-ethyl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-((2-hydroxy-ethyl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (R)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (R)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (R)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (R)-3-fluoro-4-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-3-fluoro-4-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (R)-3-fluoro-4-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-3-fluoro-4-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (R)-3-fluoro-4-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-3-fluoro-4-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (R)-3-fluoro-4-({[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-3-fluoro-4-({[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (R)-3-fluoro-4-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-3-fluoro-4-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (R)-3-fluoro-4-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-3-fluoro-4-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (R)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (R)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (R)-6-({[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (S)-6-({[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (R)-1-{2-[(S)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-{2-[(S)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)—N—((S)-9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-3-hydroxy-3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propionamide;-   (R)—N—((S)-9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-3-hydroxy-3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propionamide;-   (S)—N—((S)-9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-3-hydroxy-3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propionamide;-   (S)—N—((S)-9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-3-hydroxy-3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propionamide;-   (R)-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-6-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (S)-6-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (R)-7-fluoro-2-methoxy-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (R)-7-fluoro-2-methoxy-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (1R)-9-fluoro-1-{(3R)-3-hydroxy-3-[(5R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R)-9-fluoro-1-{(3R)-3-hydroxy-3-[(5S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R)-9-fluoro-1-{(3S)-3-hydroxy-3-[(5R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R)-9-fluoro-1-{(3S)-3-hydroxy-3-[(5S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S)-9-fluoro-1-{(3R)-3-hydroxy-3-[(5R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S)-9-fluoro-1-{(3R)-3-hydroxy-3-[(5S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S)-9-fluoro-1-{(3S)-3-hydroxy-3-[(5R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S)-9-fluoro-1-{(3S)-3-hydroxy-3-[(5S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-one;    as well as to the salts (in particular the pharmaceutically    acceptable salts) thereof.

xc) Yet further particularly preferred compounds of formula I as definedin embodiment ii) or vi) are the following compounds:

-   6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   9-bromo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-9-carbonitrile;-   4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-9-carbonitrile;-   (R)-4-oxo-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-7-carboxylic    acid ethyl ester;-   (R)-7-hydroxymethyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-4-oxo-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-1-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-7-carboxylic    acid;-   (R)-7-dimethylaminomethyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-7-pyrrolidin-1-ylmethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-7-fluoro-6-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (R)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (R)-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (R)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (R)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (R)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (R)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (R)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (R)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   9-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-(methyl-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   6-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (RS)-6-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   6-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (R)-1-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-1-{2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-{4-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-butylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-7-fluoro-6-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (1R*,2R*)-4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic    acid methyl ester;-   (1R*,2R*)-4-oxo-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic    acid methyl ester;-   (1R*,2R*)-2-hydroxymethyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R*,2R*)-2-hydroxymethyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R*,2R*)-2-methoxymethyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R*,2S*)-2-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R*,2S*)-2-methyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R*,2S*)-2-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R*,2S*)-2-methyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R*,2R*)-2-(1-hydroxy-1-methyl-ethyl)-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   N-(9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-N-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-acetamide;-   (S)-4-hydroxy-4-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   9-fluoro-1-hydroxy-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;    as well as the salts (in particular the pharmaceutically acceptable    salts) thereof.

xci) Yet a further object of this invention thus relates to thefollowing compounds of formula I as defined in embodiment ii) or vi):

-   (R)-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (S)-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (R)-9-bromo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-bromo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-9-carbonitrile;-   (S)-4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-9-carbonitrile;-   (R)-4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-9-carbonitrile;-   (S)-4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-9-carbonitrile;-   (R)-4-oxo-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-7-carboxylic    acid ethyl ester;-   (R)-7-hydroxymethyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-4-oxo-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-7-carboxylic    acid;-   (R)-7-dimethylaminomethyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-7-pyrrolidin-1-ylmethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-7-fluoro-6-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (R)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (R)-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (R)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (R)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (R)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (R)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (R)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (R)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (S)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (R)-9-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-(methyl-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-(methyl-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-6-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (S)-6-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (R)-6-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (S)-6-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (R)-6-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (S)-6-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (R)-1-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-1-{2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-{4-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-butylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-{4-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-butylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-{4-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-butylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-{4-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-butylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-7-fluoro-6-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (1R,2R)-4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic    acid methyl ester;-   (1S,2S)-4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic    acid methyl ester;-   (1R,2R)-4-oxo-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic    acid methyl ester;    -   (1S,2S)-4-oxo-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic        acid methyl ester;-   (1R,2R)-2-hydroxy    methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S,2S)-2-hydroxymethyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R,2R)-2-hydroxymethyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S,2S)-2-hydroxymethyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R,2R)-2-methoxymethyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S,2S)-2-methoxymethyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R,2S)-2-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S,2R)-2-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R,2S)-2-methyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S,2R)-2-methyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R,2S)-2-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S,2R)-2-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R,2S)-2-methyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S,2R)-2-methyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R,2R)-2-(1-hydroxy-1-methyl-ethyl)-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S,2S)-2-(1-hydroxy-1-methyl-ethyl)-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   N—((R)-9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-N-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-acetamide;-   N—((S)-9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-N-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-acetamide;-   (S)-4-hydroxy-4-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;-   (R)-9-fluoro-1-hydroxy-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-hydroxy-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;    as well as to the salts (in particular the pharmaceutically    acceptable salts) thereof.

xcii) Yet other particularly preferred compounds of formula I as definedin embodiment i) or v) are the following compounds:

-   1-({[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-chloro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-chloro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-ethyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-ethynyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R*,2R*)-9-fluoro-4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic    acid methyl ester;-   (1R*,2R*)-9-fluoro-2-hydroxymethyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R*,2S*)-9-fluoro-2-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R*,2S*)-9-fluoro-2-methyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R*,2S*)-9-fluoro-2-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R*,2R*)-9-fluoro-4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic    acid;-   9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R*,2S*)-2-aminomethyl-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1-methyl-1,2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1-(3-hydroxypropyl)-1,2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-one;    as well as the salts (in particular the pharmaceutically acceptable    salts) thereof.

xciii) Yet another object of this invention thus relates to thefollowing compounds of formula I as defined in embodiment i) or v):

-   (R)-1-({[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-({[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-chloro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-chloro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-chloro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-chloro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-ethyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-ethyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-ethynyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-ethynyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R,2R)-9-fluoro-4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic    acid methyl ester;-   (1S,2S)-9-fluoro-4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic    acid methyl ester;-   (1R,2R)-9-fluoro-2-hydroxymethyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S,2S)-9-fluoro-2-hydroxymethyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R,2S)-9-fluoro-2-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S,2R)-9-fluoro-2-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R,2S)-9-fluoro-2-methyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S,2R)-9-fluoro-2-methyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R,2S)-9-fluoro-2-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S,2R)-9-fluoro-2-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R,2R)-9-fluoro-4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic    acid;-   (1S,2S)-9-fluoro-4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic    acid;-   (R)-9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1R,2S)-2-aminomethyl-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (1S,2R)-2-aminomethyl-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (S)-9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;-   (R)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (S)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (R)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (S)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (R)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1-methyl-1,2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (S)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1-methyl-1,2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (R)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1-(3-hydroxypropyl)-1,2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-one;-   (S)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1-(3-hydroxypropyl)-1,2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-one;    as well as to the salts (in particular the pharmaceutically    acceptable salts) thereof.

xciv) The invention further relates to the compounds of formula I asdefined in embodiment i) or v) which are selected from the groupconsisting of the compounds listed in embodiment lxxxvi), the compoundslisted in embodiment lxxxviii), the compounds listed in embodiment xc)and the compounds listed in embodiment xcii), as well as to the salts(in particular the pharmaceutically acceptable salts) of such compounds.In particular, it also relates to the groups of compounds of formula Iselected from the group consisting of the compounds listed in embodimentlxxxvi), the compounds listed in embodiment lxxxviii), the compoundslisted in embodiment xc) and the compounds listed in embodiment xcii),which groups of compounds furthermore correspond to one of embodimentsix) to lxxxv), as well as to the salts (in particular thepharmaceutically acceptable salts) of such compounds.

xcv) The invention moreover relates to the compounds of formula I asdefined in embodiment i) or v) which are selected from the groupconsisting of the compounds listed in embodiment lxxxvii), the compoundslisted in embodiment lxxxix), the compounds listed in embodiment xci)and the compounds listed in embodiment xciii), as well as to the salts(in particular the pharmaceutically acceptable salts) of such compounds.In particular, it also relates to the groups of compounds of formula Iselected from the group consisting of the compounds listed in embodimentlxxxvii), the compounds listed in embodiment lxxxix), the compoundslisted in embodiment xci) and the compounds listed in embodiment xciii),which groups of compounds furthermore correspond to one of embodimentsix) to lxxxv), as well as to the salts (in particular thepharmaceutically acceptable salts) of such compounds.

The compounds of formula I according to the invention, i.e. according toone of embodiments i) to xcv) above, are suitable for the use aschemotherapeutic active compounds in human and veterinary medicine andas substances for preserving inorganic and organic materials inparticular all types of organic materials for example polymers,lubricants, paints, fibres, leather, paper and wood.

The compounds of formula I according to the invention are particularlyactive against bacteria and bacteria-like organisms. They are thereforeparticularly suitable in human and veterinary medicine for theprophylaxis and chemotherapy of local and systemic infections caused bythese pathogens as well as disorders related to bacterial infectionscomprising pneumonia, otitis media, sinusitis, bronchitis, tonsillitis,and mastoiditis related to infection by Streptococcus pneumoniae,Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus,Enterococcus faecalis, E. faecium, E. casseliflavus, S. epidermidis, S.haemolyticus, or Peptostreptococcus spp.; pharyngitis, rheumatic fever,and glomerulonephritis related to infection by Streptococcus pyogenes,Groups C and G streptococci, Corynebacterium diphtheriae, orActinobacillus haemolyticum; respiratory tract infections related toinfection by Mycoplasma pneumoniae, Legionella pneumophila,Streptococcus pneumoniae, Haemophilus influenzae, or Chlamydiapneumoniae; blood and tissue infections, including endocarditis andosteomyelitis, caused by S. aureus, S. haemolyticus, E. faecalis, E.faecium, E. durans, including strains resistant to known antibacterialssuch as, but not limited to, beta-lactams, vancomycin, aminoglycosides,quinolones, chloramphenicol, tetracyclines and macrolides; uncomplicatedskin and soft tissue infections and abscesses, and puerperal feverrelated to infection by Staphylococcus aureus, coagulase-negativestaphylococci (i.e., S. epidermidis, S. haemolyticus, etc.),Streptococcus pyogenes, Streptococcus agalactiae, Streptococcal groupsC-F (minute colony streptococci), viridans streptococci, Corynebacteriumminutissimum, Clostridium spp., or Bartonella henselae; uncomplicatedacute urinary tract infections related to infection by Staphylococcusaureus, coagulase-negative staphylococcal species, or Enterococcus spp.;urethritis and cervicitis; sexually transmitted diseases related toinfection by Chlamydia trachomatis, Haemophilus ducreyi, Treponemapallidum, Ureaplasma urealyticum, or Neiserria gonorrheae; toxindiseases related to infection by S. aureus (food poisoning and toxicshock syndrome), or Groups A, B, and C streptococci; ulcers related toinfection by Helicobacter pylori; systemic febrile syndromes related toinfection by Borrelia recurrentis; Lyme disease related to infection byBorrelia burgdorferi; conjunctivitis, keratitis, and dacrocystitisrelated to infection by Chlamydia trachomatis, Neisseria gonorrhoeae, S.aureus, S. pneumoniae, S. pyogenes, H. influenzae, or Listeria spp.;disseminated Mycobacterium avium complex (MAC) disease related toinfection by Mycobacterium avium, or Mycobacterium intracellulare;infections caused by Mycobacterium tuberculosis, M. leprae, M.paratuberculosis, M. kansasii, or M. chelonei; gastroenteritis relatedto infection by Campylobacter jejuni; intestinal protozoa related toinfection by Cryptosporidium spp.; odontogenic infection related toinfection by viridans streptococci; persistent cough related toinfection by Bordetella pertussis; gas gangrene related to infection byClostridium perfringens or Bacteroides spp.; and atherosclerosis orcardiovascular disease related to infection by Helicobacter pylori orChlamydia pneumoniae.

The compounds of formula I according to the present invention arefurther useful for the preparation of a medicament for the treatment ofinfections that are mediated by bacteria such as E. coli, Klebsiellapneumoniae and other Enterobacteriaceae, Acinetobacter spp. includingAcinetobacter baumanii, Stenothrophomonas maltophilia, Neisseriameningitidis, Bacillus cereus, Bacillus anthracis, Clostridiumdifficile, Corynebacterium spp., Propionibacterium acnes and bacteroidespp.

The compounds of formula I according to the present invention arefurther useful to treat protozoal infections caused by Plasmodiummalaria, Plasmodium falciparum, Toxoplasma gondii, Pneumocystis carinii,Trypanosoma brucei and Leishmania spp.

The present list of pathogens is to be interpreted merely as examplesand in no way as limiting.

The compounds of formula I according to this invention, or thepharmaceutically acceptable salt thereof, may be used for thepreparation of a medicament, and are suitable, for the prevention ortreatment (and notably for the treatment) of a bacterial infection.

One aspect of this invention therefore relates to the use of a compoundof formula I according to one of embodiments i) to xcv), or of apharmaceutically acceptable salt thereof, for the manufacture of amedicament for the prevention or treatment (and notably for thetreatment) of a bacterial infection. Another aspect of this inventionrelates to a compound of formula I according to one of embodiments i) toxcv), or of a pharmaceutically acceptable salt thereof, for theprevention or treatment (and notably for the treatment) of a bacterialinfection.

Accordingly, the compounds of formula I according to one of embodimentsi) to xcv), or the pharmaceutically acceptable salts thereof, may beused for the preparation of a medicament, and are suitable, for theprevention or treatment (and notably for the treatment) of a bacterialinfection selected from the group consisting of respiratory tractinfections, otitis media, meningitis, skin and soft tissue infections(whether complicated or uncomplicated), pneumonia (including hospitalacquired pneumonia), bacteremia, endocarditis, intraabdominalinfections, gastrointestinal infections, Clostridium difficileinfections, urinary tract infections, sexually transmitted infections,foreign body infections, osteomyelitis, lyme disease, topicalinfections, opthalmological infections, tuberculosis and tropicaldiseases (e.g. malaria), and notably for the prevention or treatment(especially for the treatment) of a bacterial infection selected fromthe group consisting of respiratory tract infections, otitis media,meningitis, skin and soft tissue infections (whether complicated oruncomplicated), pneumonia (including hospital acquired pneumonia) andbacteremia.

As well as in humans, bacterial infections can also be treated usingcompounds of formula I (or pharmaceutically acceptable salts thereof) inother species like pigs, ruminants, horses, dogs, cats and poultry.

The present invention also relates to pharmacologically acceptable saltsand to compositions and formulations of compounds of formula I.

Any reference to a compound of formula I is to be understood asreferring also to the salts (and especially the pharmaceuticallyacceptable salts) of such compounds, as appropriate and expedient.

A pharmaceutical composition according to the present invention containsat least one compound of formula I (or a pharmaceutically acceptablesalt thereof) as the active agent and optionally carriers and/ordiluents and/or adjuvants, and may also contain additional knownantibiotics.

The compounds of formula I and their pharmaceutically acceptable saltscan be used as medicaments, e.g. in the form of pharmaceuticalcompositions for enteral or parenteral administration.

The production of the pharmaceutical compositions can be effected in amanner which will be familiar to any person skilled in the art (see forexample Remington, The Science and Practice of Pharmacy, 21st Edition(2005), Part 5, “Pharmaceutical Manufacturing” [published by LippincottWilliams & Wilkins]) by bringing the described compounds of formula I ortheir pharmaceutically acceptable salts, optionally in combination withother therapeutically valuable substances, into a galenicaladministration form together with suitable, non-toxic, inert,therapeutically compatible solid or liquid carrier materials and, ifdesired, usual pharmaceutical adjuvants.

Another aspect of the invention concerns a method for the prevention orthe treatment (and notably for the treatment) of a bacterial infectionin a patient comprising the administration to said patient of apharmaceutically active amount of a compound of formula I according toone of embodiments i) to xcv), or a pharmaceutically acceptable salt ofsuch a compound.

Besides, any preferences and (sub-)embodiments indicated for thecompounds of formula I (whether for the compounds themselves, saltsthereof, compositions containing the compounds or salts thereof, uses ofthe compounds or salts thereof, etc.) apply mutatis mutandis tocompounds of formula I_(CE), I_(P1), I_(CEP1), I_(P2), I_(CEP2), I_(P3)or I_(CEP3).

Moreover, the compounds of formula I may also be used for cleaningpurposes, e.g. to remove pathogenic microbes and bacteria from surgicalinstruments or to make a room or an area aseptic. For such purposes, thecompounds of formula I could be contained in a solution or in a sprayformulation.

The compounds of formula I can be manufactured in accordance with thepresent invention using the procedures described hereafter.

Preparation of Compounds of Formula I ABBREVIATIONS

The following abbreviations are used throughout the specification andthe examples:

-   Ac acetyl-   AcOH acetic acid-   AD-mix α 1,4-bis(dihydroquinine)phthalazine, K₃Fe(CN)₆, K₂CO₃ and    K₂OsO₄.2H₂O-   AD-mix β 1,4-bis(dihydroquinidine)phthalazine, K₃Fe(CN)₆, K₂CO₃ and    K₂OsO₄.2H₂O-   Alloc allyloxycarbonyl-   AIBN azobisisobutyronitrile-   aq. aqueous-   9-BBN 9-borabicyclo[3.3.1]nonane-   Boc tert-butoxycarbonyl-   Bs 4-bromobenzenesulfonyl (brosylate)-   Bu n-butyl-   Cbz benzyloxycarbonyl-   CC column chromatography over silica gel-   CDI 1,1′-carbonyldiimidazole-   DAD diode array detection-   DBU 1,8-diazabicyclo[5.4.0]undec-7-ene-   DCC N,N′-dicyclohexylcarbodiimide-   DCE 1,2-dichloroethane-   DEA diethylamine-   DCM dichloromethane-   (DHQ)₂PHAL 1,4-bis(dihydroquinine)phthalazine-   (DHQD)₂PHAL 1,4-bis(dihydroquinidine)phthalazine-   DIAD diisopropylazodicarboxylate-   DIBAH diisobutylaluminium hydride-   DIPEA N,N-diisopropylethylamine-   DMAP 4-dimethylaminopyridine-   DMF N,N-dimethylformamide-   DMSO dimethylsulfoxide-   DPEphos bis(2-diphenylphosphinophenyl)ether-   DPPA diphenyl phosphorylazide-   EA ethyl acetate-   EDC 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride-   ee enantiomeric excess-   ELSD Evaporative Light Scattering Detector-   ESI Electron Spray Ionisation-   eq. equivalent-   ether diethyl ether-   Et ethyl-   EtOH ethanol-   Fmoc 9-fluorenylmethoxycarbonyl-   HATU O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium    hexafluorophosphate-   Hept heptane-   Hex hexane-   HOBT 1-hydroxybenzotriazole hydrate-   HPLC high pressure liquid chromatography-   HV high vacuum-   KHMDS potassium hexamethyldisilazide-   LAH lithium aluminium hydride-   LC liquid chromatography-   LDA lithium diisopropylamide-   LiHMDS lithium hexamethyldisilazide-   MCPBA meta-chloroperbenzoic acid-   Me methyl-   MeCN acetonitrile-   MeOH methanol-   MS Mass Spectroscopy-   Ms methanesulfonyl (mesyl)-   n-BuLi n-butyl lithium-   NBS N-bromosuccinimide-   Nf nonafluorobutanesulfonyl-   Ns 4-nitrobenzenesulfonyl (nosylate)-   NMO N-methyl-morpholine N-oxide-   org. organic-   o-Tol ortho-tolyl-   Pd/C palladium on carbon-   Pd(OH)₂/C palladium dihydroxide on carbon-   Ph phenyl-   Pht phthaloyl-   Pyr pyridine-   quant. quantitative-   rac racemic-   rt room temperature-   sat. saturated-   TBAF tetrabutylammonium fluoride-   TBDMS tert-butyldimethylsilyl-   TBME tert-butylmethylether-   TBDPS tert-butyldiphenylsilyl-   tBu tert-butyl-   TEA triethylamine-   TEMPO 2,2,6,6-tetramethyl-1-piperidinyloxy-   Tf trifluoromethanesulfonyl (triflyl)-   TFA trifluoroacetic acid-   THF tetrahydrofuran-   TLC thin layer chromatography-   TMEDA tetramethylethylenediamine-   TMS trimethylsilyl-   t_(R) retention time-   Ts para-toluenesulfonyl    General Reaction Techniques:    General Reaction Technique 1 (Alkylation of an Amine):

Ammonia or the appropriate amine derivatives is/are reacted with theappropriate derivatives having a side group L¹, L², L³ or L⁴, whereinL¹, L², L³ or L⁴ represents OMs, OTf, OTs, ONs, ONf, OBs, Cl, Br or I,in presence of an inorganic base such as K₂CO₃ or an org. base such asTEA in a solvent such as THF, DMF or DMSO between 0° C. and +80° C.Further details can be found in Comprehensive Organic Transformations. Aguide to Functional Group Preparations; 2^(nd) Edition, R. C. Larock,Wiley-VC; New York, Chichester, Weinheim, Brisbane, Singapore, Toronto,(1999). Section Amines p. 779.

General Reaction Technique 2 (Reductive Amination):

A solution of amine (1 mmol) and aldehyde or ketone (1 mmol) in DCE/MeOH1:1 (10 mL) is stirred at rt overnight possibly in presence of adessicant such as MgSO₄ or 3 Å molecular sieves. NaBH₄ (2-5 eq.) isadded and the reaction allowed to proceed for one hour. The reaction isdiluted with DCM and aq. NH₄OH. The org. phase is washed with water,dried over MgSO₄ and concentrated. Alternatively, a solution of amine (1mmol) and aldehyde or ketone (1 mmol) in DCE/MeOH 1:1 (10 mL) is treatedwith NaBH(OAc)₃ (2 eq.). The mixture is stirred at rt until completeconversion. The reaction is diluted with DCM and aq. NH₄OH. The org.phase is washed with water, dried over MgSO₄ and concentrated.

General Reaction Technique 3 (Activation of an Alcohol):

The alcohol is reacted with MSCl, TfCl, NfCl, NsCl, BsCl or TsCl inpresence of an organic base such as TEA, DIPEA or Pyr in a dry aproticsolvent such as DCM, THF or Pyr between −10° C. and rt. Alternatively,the alcohol can also be reacted with Ms₂O or Tf₂O. The activatedintermediate can be further transformed into its corresponding iodo orbromo derivative by reaction of the activated alcohol with NaI or NaBrin a solvent such as acetone.

General Reaction Technique 4 (Removal of Amino Protecting Groups):

The benzyl carbamates are deprotected by hydrogenolysis over a noblemetal catalyst (e.g. Pd/C or Pd(OH)₂/C). The Boc group is removed underacidic conditions such as HCl in an organic solvent such as MeOH ordioxane, or TFA neat or diluted in a solvent such DCM. Further generalmethods to remove amine protecting groups have been described in T. W.Greene, P. G. M. Wuts, Protecting Groups in Organic Synthesis, 3^(rd) Ed(1999), 494-653 (Publisher: John Wiley and Sons, Inc., New York, N.Y.).

General Reaction Technique 5 (Ester, Ketone or Aldehyde Reduction):

The ester is reduced with a boron or aluminium hydride reducing agentsuch as LiBH₄ or LAH in a solvent such as THF between −20° C. and 40° C.Alternatively, the ester function is hydrolyzed into its correspondingacid using an alkali hydroxide such as NaOH, KOH or LiOH in water or ina mixture of water with polar protic or aprotic organic solvent such asTHF or MeOH between −10° C. and 50° C. The resulting carboxylic acid isfurther reduced into the corresponding alcohol using a borane derivativesuch as a BH₃.THF complex in a solvent such as THF between −10° C. and40° C.

The aldehyde and the ketone are reduced with a boron or aluminiumhydride reducing agent such as NaBH₄, LiBH₄ or LAH in a solvent such asTHF between −20° C. and 40° C. Further details can be found inComprehensive Organic Transformations. A guide to Functional GroupPreparations; 2nd Edition, R. C. Larock, Wiley-VC; New York, Chichester,Weinheim, Brisbane, Singapore, Toronto, (1999). Section Alcohols andphenols, p. 1057-1087.

General Reaction Technique 6 (Cis-Dihydroxylation):

The diol is obtained by dihydroxylation of the corresponding ethylenicderivative using a catalytic amount of potassium osmate in the presencea co-oxidant such as NMO in an aq. solvent such as an acetone-water orDCM-water mixture (see Cha, J. K., Chem. Rev. (1995), 95, 1761-1795).The chiral cis-diols are obtained by using AD-mix α or AD-mix β inpresence of methanesulfonamide in a water/2-methyl-2 propanol mixture asdescribed in Chem. Rev. (1994), 94, 2483. The sense of induction relieson the chiral ligand contained in the AD mixture, either adihydroquinine-based ligand in AD-mix α or a dihydroquinidine-basedligand in AD-mix β.

General Reaction Technique 7 (Protection of Alcohols):

The alcohols are protected as silyl ethers (usually TBDMS or TBDPSethers). The alcohol is reacted with the required silyl chloride reagent(TBDMSCl or TBDPSCl) in presence of a base such as imidazole or TEA in asolvent such as DCM or DMF between +10° C. and +40° C. Furtherstrategies to introduce other alcohol protecting groups have beendescribed in T. W. Greene, P. G. M. Wuts, Protecting Groups in OrganicSynthesis, 3rd Ed (1999), 23-147 (Publisher: John Wiley and Sons, Inc.,New York, N.Y.).

General Reaction Technique 8 (Removal of Hydroxy Protecting Groups):

The silyl ether groups are removed either using fluoride anion sourcessuch as TBAF in THF between 0° C. and +40° C. or HF in MeCN between 0°C. and +40° C. or using acidic conditions such as AcOH in THF/MeOH orHCl in MeOH. Further methods to remove the TBDMS and TBDPS groups aregiven in T. W. Greene, P. G. M. Wuts, Protecting Groups in OrganicSynthesis, 3^(rd) Ed (1999), 133-139 and 142-143 respectively(Publisher: John Wiley and Sons, Inc., New York, N.Y.). Further generalmethods to remove alcohol protecting groups are described in T. W.Greene, P. G. M. Wuts, Protecting Groups in Organic Synthesis, 3^(rd) Ed(1999), 23-147 (Publisher: John Wiley and Sons, Inc., New York, N.Y.).In the particular case of alkylcarboxy protecting group, the freealcohol can be obtained by the action of an inorganic base such as K₂CO₃in a solvent such as MeOH.

General Reaction Technique 9 (Formation of Aldehydes):

The alcohols can be transformed into their corresponding aldehydesthrough oxidation under Swern (see D. Swern et al., J. Org. Chem.(1978), 43, 2480-2482) or Dess Martin (see D. B. Dess and J. C. Martin,J. Org. Chem. (1983), 48, 4155) conditions respectively. Alternatively,the esters can be transformed into their corresponding aldehydes bycontrolled reduction with a bulky hydride reagent such as DIBAH.

General Reaction Technique 10 (Amine Protection):

Amines are usually protected as carbamates such as Alloc, Cbz, Boc orFmoc. They are obtained by reacting the amine with allyl or benzylchloroformate, di tert-butyl dicarbonate or FmocCl in presence of a basesuch as NaOH, TEA, DMAP or imidazole. They can also be protected asN-benzyl derivatives by reaction with benzyl bromide or chloride inpresence of a base such as Na₂CO₃ or TEA. Alternatively, N-benzylderivatives can be obtained through reductive amination in presence ofbenzaldehyde and a borohydride reagent such as NaBH₄, NaBH₃CN orNaBH(OAc)₃ in a solvent such as MeOH, DCE or THF. Further strategies tointroduce other amine protecting groups have been described in T. W.Greene, P. G. M. Wuts, Protecting Groups in Organic Synthesis, 3rd Ed(1999), 494-653 (Publisher: John Wiley and Sons, Inc., New York, N.Y.).

General Reaction Technique 11 (Hydrogenation of a Double Bond):

The unsaturated derivatives dissolved in a solvent such as MeOH, EA orTHF are hydrogenated over a noble metal catalyst such as Pd/C or PtO₂,or over Raney Ni. At the end of the reaction the catalyst is filteredoff and the filtrate is evaporated under reduced pressure. Alternativelythe reduction can be performed by catalytic transfer hydrogenation usingPd/C and ammonium formate as hydrogen source.

General Reaction Technique 12 (Reduction of Azides into Amines):

The azides are hydrogenated over a noble metal catalyst such as Pd/C insolvent such as MeOH or EA. In case the molecule is containing anunsaturated double or triple bond, the reduction can be performed usingPPh₃ in presence of water as described in J. Med. Chem. (1993), 36,2558-68.

General Reaction Technique 13 (Amide Formation):

The carboxylic acid is reacted with the amine in presence of anactivating agent such as DCC, EDC, HOBT, n-propylphosphonic cyclicanhydride, HATU or di-(N-succinimidyl)-carbonate, in a dry aproticsolvent such as DCM, MeCN or DMF between −20° C. and +60° C. (see G.Benz in Comprehensive Organic Synthesis, B. M. Trost, I. Fleming, Eds;Pergamon Press: New York (1991), vol. 6, p. 381). Alternatively, thecarboxylic acid can be activated by conversion into its correspondingacid chloride by reaction with oxalyl chloride or thionyl chloride neator in a solvent like DCM between 20° and +60° C. Further activatingagents can be found in Comprehensive Organic Transformations. A guide toFunctional Group Preparations; 2nd Edition, R. C. Larock, Wiley-VC; NewYork, Chichester, Weinheim, Brisbane, Singapore, Toronto, 1999. Sectionnitriles, carboxylic acids and derivatives p. 1941-1949.

General Reaction Technique 14 (Oxidation of Alcohols/Aldehydes intoAcids):

Aldehydes can be oxidized into their corresponding acids by a variety ofmethods as described in Comprehensive Organic Transformations. A guideto Functional Group Preparations; 2nd Edition, R. C. Larock, Wiley-VC;New York, Chichester, Weinheim, Brisbane, Singapore, Toronto, 1999.Section nitriles, carboxylic acids and derivatives, p. 1653-1655. Amongthem, potassium permanganate in an acetone-water mixture (see Synthesis1987, 85) or sodium chlorite in 2-methyl-2-propanol in presence of2-methyl-2-butene (see Tetrahedron 1981, 37, 2091-2096) are frequentlyused.

Alcohols can be directly oxydized into their corresponding acids by avariety of methods as described in Comprehensive OrganicTransformations. A guide to Functional Group Preparations; 2nd Edition,R. C. Larock, Wiley-VC; New York, Chichester, Weinheim, Brisbane,Singapore, Toronto, 1999. Section nitriles, carboxylic acids andderivatives p. 1646-1648. Among them, [bis(acetoxy)iodo]benzene inpresence of TEMPO, the Jones reagents (CrO₃/H₂SO₄), NaIO₄ in presence ofRuCl₃, KMnO₄ or pyridine H₂Cr₂O₇ are frequently used.

General Preparation Methods:

Preparation of the Compounds of Formula I:

The compounds of formula I can be manufactured by the methods givenbelow, by the methods given in the examples or by analogous methods.Optimum reaction conditions may vary with the particular reactants orsolvents used, but such conditions can be determined by a person skilledin the art by routine optimisation procedures.

Sections a) to r) hereafter describe general methods for preparingcompounds of formula I. If not indicated otherwise, the generic groupsor integers n, p, R⁰, R¹, U, V, R⁴, R⁵, R², A and G are as defined forformula I. General synthetic methods used repeatedly throughout the textbelow are referenced to and described in the above section entitled“General synthetic methods”. Other abbreviations used are defined in theexperimental section. In some instances the generic groups R⁰, R¹, R²,R⁴, R⁵, U, A and G might be incompatible with the assembly illustratedin the procedures and schemes below and so will require the use ofprotecting groups. The use of protecting groups is well known in the art(see for example “Protective Groups in Organic Synthesis”, T. W. Greene,P. G. M. Wuts, Wiley-Interscience, 1999).

-   a) The compounds of formula I wherein R² represents H and A    represents —(CH₂)_(p)— can be manufactured in accordance with the    present invention by reacting the compounds of formula II

-    with the compounds of formula III

-    wherein L¹ is a halogen such as bromine or iodine, or a group    OSO₂R^(a) wherein R^(a) is alkyl, CF₃ or tolyl, following general    reaction technique 1.-   b) The compounds of formula I wherein R² represents H and A    represents —CH₂CH₂CH(OH)— or —(CH₂)_(p)—, p being 3 or 4, can be    manufactured in accordance with the present invention by reacting    the compounds of formula II as defined in section a) with the    aldehydes of formula IV

-    wherein A′ represents —(CH₂)_(p-1)— or —CH₂CH(OPG)-, PG being a    silyl protecting group such as TBDMS or TBDPS, following general    reaction technique 2, the compounds thus obtained being if necessary    deprotected using general reaction technique 8.-   c) The compounds of formula I wherein R² represents H, n represents    1 or 2 and A represents —(CH₂)_(p)—, p being 1, 2 or 3, can further    be manufactured in accordance with the present invention by reacting    the compounds of formula V

-    wherein L² is a halogen such as bromine or iodine, or a group    OSO₂R^(a) wherein R^(a) is alkyl, CF₃ or tolyl, with the amines of    formula VI

-    following general reaction technique 1.-   d) The compounds of formula I wherein R² represents H, A represents    —(CH₂)_(p)— and n is 1 or 2 can be manufactured in accordance with    the present invention by reacting the compounds of formula VII

-    with the previously mentioned amines of formula VI following    general reaction technique 2.-   e) The compounds of formula I wherein “-----” is absent, R⁰    represents H and U is CH₂ or NH can be obtained by hydrogenation of    a compound of formula I wherein “-----” is a bond and U is CH or N    over a noble metal catalyst such as Pd/C, following general reaction    technique 11. In the case wherein U is N the transformation can also    be performed by reduction with a hydride reagent such as NaBH₄.-   f) The compounds of formula I wherein each of R⁴ and R⁵ represents H    and A represents —(CH₂)_(p)— can moreover be obtained by reacting    the compounds of formula VIII

-    wherein R²⁰ represents H, CH₂R³′ or an amino protecting group such    as Cbz, Boc or Fmoc and R³′ represents hydrogen or (C₁-C₃)alkyl or    also R³′ represents a (C₁-C₃)hydroxyalkyl group the hydroxy of which    is protected in the form of a silyl ether (e.g. as a TBDMS or TBDPS    ether), with the compounds of formula IX    G-L³   IX-    wherein L³ represents halogen. In the case of compounds of formula    IX wherein G is a group G¹ and X is N or G is a group G² and Y¹    and/or Y³ is/are N, the reaction can be performed in the presence of    NaH. This reaction can also be performed under conditions described    for the metal catalyzed N-arylation of 2-oxazolidinones or amides.    In particular by using CuI and 1,1,1-tris(hydroxymethyl)ethane in    presence of Cs₂CO₃ (Org. Lett. (2006), 8, 5609-5612), or Pd(OAc)₂    and DPEphos in presence of K₃PO₄. The compounds thus obtained are if    necessary deprotected using general reaction technique 8.-   g) The compounds of formula I wherein R² does not represent H can    furthermore be obtained by reacting the compounds of formula X

-    wherein A′ represents —(CH₂)_(p)— or —CH₂CH₂CH(OPG)-, PG being a    silyl protecting group such as TBDMS or TBDPS, with the compounds of    formula XI    R³′—CH₂-L⁴   XI-    wherein L⁴ represents halogen or the group OSO₂R^(a) wherein R^(a)    is alkyl, CF₃ or tolyl and R³′ represents hydrogen or (C₁-C₃)alkyl    or also R³′ represents a (C₁-C₃)hydroxyalkyl group, the hydroxy of    which is protected in the form of a silyl ether (e.g. as a TBDMS or    TBDPS ether), following general reaction technique 1, the compounds    thus obtained being if necessary deprotected using general reaction    technique 8. In the particular case wherein R³′ is H, the reaction    can also be performed by reaction of the compounds of formula X as    defined above with dimethylsulfate.-   h) The compounds of formula I wherein R² does not represent H can    also be obtained by reacting the compounds of formula X as defined    above with the compounds of formula XII    R³′—CHO   XII-    wherein R³′ represents hydrogen or (C₁-C₃)alkyl or also R³′    represents a (C₁-C₃)hydroxyalkyl group, the hydroxy of which is    protected in the form of a silyl ether (e.g. as a TBDMS or TBDPS    ether), following general reaction technique 2, the compounds thus    obtained being if necessary deprotected using general reaction    technique 8.-   i) The compounds of formula I wherein R² does not represent H can    also be obtained by reacting the compounds of formula X as defined    above with the compounds of formula XIla    R³′—CO-L⁵   XIIa-    wherein R³′ represents (C₁-C₃)alkyl or (C₁-C₃)hydroxyalkyl group,    the hydroxy of which is protected in the form of a silyl ether (e.g.    as a TBDMS or TBDPS ether) and L⁵ represents halogen or OH,    following general reaction technique 13; the compounds thus obtained    being if necessary deprotected using general reaction technique 8.    In the particular case wherein R³′ is methyl, the reaction can also    be performed by reacting the compounds of formula X as defined above    with acetic acid anhydride.-   j) The compounds of formula I wherein R² does not represent H can    furthermore be obtained by reacting the compounds of formula XIII

-    wherein R³′ represents hydrogen or (C₁-C₃)alkyl or also R³′    represents a (C₁-C₃)hydroxyalkyl group, the hydroxy of which is    protected in the form of a silyl ether (e.g. as a TBDMS or TBDPS    ether), with the compounds of formula XIV

-    wherein A′ represents —(CH₂)_(p-1)— or —CH₂CH(OPG)-, PG being a    silyl protecting group such as TBDMS or TBDPS, following general    reaction technique 13, the compounds thus obtained being if    necessary deprotected using general reaction technique 8.-   k) The compounds of formula I wherein R² does not represent H can be    obtained by reacting the compounds of formula XIII as defined above    with the compounds of formula III as defined above following general    reaction technique 1. The compounds thus obtained being if necessary    deprotected using general reaction technique 8.-   l) The compounds of formula I wherein R² does not represent H can    furthermore be obtained by reacting the compounds of formula V with    the compounds of formula XV

-    wherein R³′ represents hydrogen or (C₁-C₃)alkyl or also R³′    represents a (C₁-C₃)hydroxyalkyl group, the hydroxy of which is    protected in the form of a silyl ether (e.g. as a TBDMS or TBDPS    ether), following general reaction technique 1, the compounds thus    obtained being if necessary deprotected using general reaction    technique 8.-   m) The compounds of formula I wherein R² does not represent H can be    obtained by reacting the compounds of formula VII as defined above    with the compounds of formula XV as defined above following general    reaction technique 2, the compounds thus obtained being if necessary    deprotected using general reaction technique 8.-   n) The compounds of formula I wherein V is CR⁶ and R⁶ represents    carboxy can be obtained by hydrolysis of the derivatives of formula    I wherein R⁶ represents either alkoxycarbonyl (under acidic or basic    conditions) or benzyloxycarbonyl (under hydrogenolysis conditions).-   o) The compounds of formula I wherein V is CR⁶ and R⁶ represents    —CH₂OH can be obtained by reduction of the derivatives of formula I    wherein R⁶ represents either alkoxycarbonyl or benzyloxycarbonyl    using general reaction technique 5.-   p) The compounds of formula I wherein R⁵ represents carboxy can be    obtained from the corresponding compounds of formula I wherein R⁵    represents (C₁-C₃)alkoxycarbonyl by treatment with an aq. HCl    solution.-   q) The compounds of formula I wherein R⁵ represents    (C₁-C₃)aminoalkyl can be obtained by reacting the compounds of    formula XVI

-    wherein z represents an integer from 1 to 3 and L⁶ represents    halogen or the group OSO₂R^(a) wherein R^(a) is alkyl, CF₃ or tolyl,    with sodium azide followed by transforming the intermediate azides    into the corresponding amines of formula I using general reaction    technique 12.-   r) The compounds of formula I wherein “----” is absent, U represents    NR⁹, R⁹ represents (C₁-C₃)alkyl, 2-hydroxy-ethyl, 2-hydroxy-propyl    or 3-hydroxy-propyl, R⁰ represents H, R² represents H and A    represents —(CH₂)_(p)— or —CH₂CH₂CH(OH)— can be obtained by removal    of the amino protecting group PG⁰ from the compounds of formula XVII

-    wherein PG⁰ represents an amino protecting group such as Ac, Boc,    Cbz or Fmoc and R⁹′ represents (C₁-C₃)alkyl or also R⁹′ represents a    2-hydroxy-ethyl, 2-hydroxy-propyl or 3-hydroxy-propyl group, the    hydroxy of which group has been protected in the form of a silyl    ether (e.g. as a TBDMS or TBDPS ether), using general reaction    technique 4, this reaction being followed, in the case wherein R⁹′    is a (C₂-C₃)hydroxyalkyl group, the hydroxy group of which has been    protected in the form of a silyl ether, by removal of the silyl    protecting group using general reaction technique 8.

With reference to the reactions mentioned at preceding sections a) tor), in addition to the cases already indicated, the use of hydroxy oramino protecting groups (see general reaction techniques 7 and 8 forhydroxy protecting groups and general reaction techniques 10 and 4 foramino protecting groups) is likely to be required in the followingcases:

-   -   when R⁵ represents (C₁-C₃)hydroxyalkyl or (C₁-C₃)aminoalkyl;    -   when R⁶ represents (C₁-C₃)hydroxyalkyl or a group        —(CH₂)_(q)—NR⁷R⁸ wherein at least one of R⁷ and R⁸ represents H;    -   when “----” is absent and U represents NR⁹ wherein R⁹ represents        2-hydroxy-ethyl, 2-hydroxy-propyl or 3-hydroxy-propyl.

The compounds of formula I thus obtained may, if desired, be convertedinto their salts, and notably into their pharmaceutically acceptablesalts.

Besides, whenever the compounds of formula I are obtained in the form ofmixtures of enantiomers, the enantiomers can be separated using methodsknown to one skilled in the art, e.g. by formation and separation ofdiastereomeric salts or by HPLC over a chiral stationary phase such as aRegis Whelk-O1(R,R) (10 μm) column, a Daicel ChiralCel OD-H (5-10 μm)column, or a Daicel ChiralPak IA (10 μm) or AD-H (5 μm) column. Typicalconditions of chiral HPLC are an isocratic mixture of eluent A (EtOH, inpresence or absence of an amine such as triethylamine, diethylamine) andeluent B (hexane), at a flow rate of 0.8 to 150 mL/min. Whenever thecompounds of formula I are obtained in the form of mixtures ofdiasteromers they may be separated by an appropriate combination ofsilica gel chromatography, HPLC and crystallization techniques.

Preparation of the Compounds of Formulae II to XV

The compounds of formula II can be prepared either by reaction of thecompounds of formula V with sodium azide followed by transformation intothe corresponding amines of formula II using general reaction technique12 or as described in Schemes 1, 1a, 1b, 1c, 1d and 1e hereafter.

The compounds of formula II wherein each of R⁴ and R⁵ represents H canbe prepared as described in Scheme 1 hereafter.

In Scheme 1, PG¹ represents an amino protecting group such as Boc orFmoc and R^(a) represents alkyl, CF₃ or tolyl.

The protected amino alcohol derivatives of formula I-1 can betransformed into the corresponding mesylates, triflates or tosylatesusing general reaction technique 3. The resulting sulfonates of formulaI-2 can be ring closed between rt and 110° C. affording the tricyclicderivatives of formula I-3. Then the amino protecting group can beremoved using general reaction technique 4 to give the compounds offormula II wherein “-----” is a bond.

The compounds of formula II wherein “-----” is absent and U representsCH₂ or NH can be prepared by using derivatives identical to thecompounds of formula I-1 except that U represents CH or N and PG¹represents Cbz. The same synthetic sequence can be used, except that,during the last step, the hydrogenation reaction reduces both the CH═CHor CH═N double bond and removes the Cbz protecting group. In the case ofcompounds of formula II wherein “-----” is absent and U represents NH,the reduction of the CH═N double bond can also be carried out using ahydride reagent such as NaBH₄.

The compounds of formula II wherein R⁴ represents H and R⁵ represents(C₁-C₃)alkyl, (C₁-C₃)hydroxyalkyl, (C₁-C₃)alkoxy(C₁-C₃)alkyl or(C₁-C₃)alkoxycarbonyl can be prepared as described in Scheme 1ahereafter.

In Scheme 1a, PG² represents an amino protecting group such as Boc orFmoc, R^(b) represents alkyl or benzyl, R^(c) represents hydrogen oralkyl and each of R^(d) and R^(e) represents alkyl.

The compounds of formula II wherein R⁴ represents H and R⁵ is(C₁-C₃)alkoxycarbonyl can be obtained by oxyamination of the acrylatederivatives of formula Ia-1 (K₂OsO₄, BocNClNa and either (DHQD)₂PHAL or(DQD)₂PHAL as described in J. Org. Chem. (2005), 70, 2847-2850). Theintermediates of formula Ia-2 can be cyclised into the derivatives offormula Ia-3 using general reaction technique 3 (including heating at50-70° C.). The corresponding compounds of formula II can then beobtained by removal of the protecting group using general reactiontechnique 4.

The compounds of formula II wherein R⁵ is hydroxymethyl can be obtainedby reduction of the ester function of the intermediates of formula Ia-3using general reaction technique 5. The corresponding compounds offormula II can then be obtained by removal of the protecting group inthe compounds of formula Ia-4 using general reaction technique 4.

The compounds of formula II wherein R⁵ is methyl can be obtained byactivation of the alcohol function of intermediates Ia-4 using generalreaction technique 3 followed by reaction with a hydride reagent such asLAH or Bu₃SnH. More generally, the compounds of formula II wherein R⁵ is(C₁-C₃)alkyl can be obtained by oxidation of the intermediates offormula Ia-4 into the corresponding aldehydes following general reactiontechnique 9 followed by sequential Wittig reaction with alkylidenetriphenylphosphorane and catalytic hydrogenation following generalreaction technique 11. The protecting group of the intermediates offormula Ia-5 thus obtained can then be removed using general reactiontechnique 4, providing the corresponding compounds of formula II.

The compounds of formula II wherein R⁵ is alkoxymethyl can be obtainedby reacting the anions of the compounds of formula Ia-4 (generated byreaction with NaH) with the corresponding halogenides of formula R^(d)—X(R^(d) being alkyl and X being halogen). The protecting group of theintermediates of formula Ia-6 thus obtained can then be removed usinggeneral reaction technique 4, providing the corresponding compounds offormula II.

The compounds of formula II wherein R⁵ is dialkylhydroxymethyl can beobtained reacting the esters of formula Ia-3 with a Grignard reagent offormula R^(e)—MgX wherein R^(e) is alkyl and X represents halogen. Theprotecting group of the intermediates of formula Ia-7 thus obtained canthen be removed using general reaction technique 4, providing thecorresponding compounds of formula II.

The compounds of formulae II and V wherein R⁴ represents OH can beprepared as described in Scheme 1b hereafter.

Accordingly, the compounds of formula V wherein R⁴ represents OH and nis 1 or 2 can be obtained by activation of the primary alcohols offormula Ib-1 or Ib-2 using general reaction technique 3 followed byreaction with NaN₃. The compounds of formula V can then be transformedinto the amines of formula II using general reaction technique 12.

Besides, the compounds of formula II wherein each of R⁴ and R⁵represents H and V represents CR⁶, R⁶ representing hydroxymethyl or agroup —CH₂—NR⁷R⁸, can be prepared as described in Scheme 1c hereafter.

In Scheme 1c, PG¹ represents an amino protecting group such as Boc orFmoc, R^(f) represents alkyl, each of R⁷ and R⁸ independently representsH or (C₁-C₃)alkyl or R⁷ and R⁸ together with the nitrogen atom bearingthem form a pyrrolidinyl, piperidinyl, morpholinyl or thiomorpholinylring.

The compounds of formula II wherein each of R⁴ and R⁵ represents H, V isCR⁶ and R⁶ represents a group —CH₂—NR⁷R⁸ can be obtained (Scheme 1c) byreducing the compounds of formula I-3 wherein V is CR⁶ and R⁶ represents(C₁-C₃)alkoxycarbonyl using general reaction technique 5, followed byeither sequential activation of the alcohol group of the intermediatesof formula Ic-1 using general reaction technique 3 and reaction with theamines of formula NHR⁷R⁸ using general reaction technique 1, or,depending on the nature of R⁷ and R⁸, by oxidation of the intermediatesof formula Ic-1 using general reaction technique 9 followed by reductiveamination using general reaction technique 2. The correspondingcompounds of formula II can then be obtained by removal of theprotecting group using general reaction technique 4.

The derivatives of formula II wherein each of R⁴ and R⁵ represents H, Vis CR⁶ and R⁶ represents either —(CH₂)_(q)—NR⁷R⁸ or —(CH₂)_(q)—OHwherein q is 2 or 3 can be obtained by similar methods wherein thecompounds of formula Ic-1 are oxidized into their correspondingaldehydes and further transformed into their homologous aldehydes byreaction with Ph₃P═CH—OMe or Ph₃P═CH—CHO followed by hydrolysis orhydrogenolysis respectively. These homologous aldehydes can be furtherprocessed affording the desired compounds of formula II wherein q is 2or 3.

The compounds of formula II wherein n is 0 and each of R⁴ and R⁵represents H can be prepared as described in Scheme 1d hereafter.

In Scheme 1d, PG³ represents an alcohol protecting group such as TBDMSor TBDPS and R^(a) represents alkyl, CF₃ or tolyl.

The vinylic derivatives of formula Id-1 can be transformed (Scheme 1d)into the corresponding diol derivatives of formula Id-2 using generalreaction technique 6. The resulting diols can selectively be transformedinto the corresponding monomesylates or monotosylates using generalreaction technique 3 and the secondary alcohol function can then beprotected using general reaction technique 7, affording the protectedderivatives of formula Id-3 which can be cyclised under thermalconditions. The alcohol protecting group in the compounds of formulaId-4 can be removed using general reaction technique 8, affording thefree alcohols of formula Id-5. The corresponding compounds of formula IIcan be obtained after formation of the corresponding azide derivatives(by reaction with DPPA under Mitsunobu conditions; see Synthesis(1981), 1) followed by formation of the corresponding amines usinggeneral reaction technique 12. The compounds of formula Id-5 wherein R⁰is H can also be obtained by dihydroxylation of the vinyl derivatives offormula Id-6 using general reaction technique 6 followed by formationthe corresponding carbonate derivatives of formula Id-8 after reactionwith CDI or triphosgene and final treatment with a base such as Cs₂CO₃.The compounds of formulae Id-4, Id-5 and II wherein “-----” is absentand U represents CH₂ or NH can be obtained by hydrogenation of thecorresponding compounds of formulae Id-4, Id-5 and II wherein “-----” isa bond and U represents CH or N.

The compounds of formula II wherein R¹ represents ethynyl can beprepared as shown in Scheme 1e hereafter.

In Scheme 1e, Hal represents a halogen atom such as bromine and PG⁴represents an amino protecting group such as Boc or Fmoc.

The compounds of formula Ie-1 can be treated between +50° C. and +110°C. with ethynyl-trimethylsilane in the presence of PdCl₂(PPh₃)₂, CuI anda base like TEA in a solvent like dioxane, affording the compounds offormula Ie-2. The compounds of formula II wherein R¹ represents ethynylcan then be obtained from the compounds of formula Ie-2 after removal ofthe TMS group using TBAF in a solvent like THF and removal of the aminoprotecting group using general reaction technique 4.

The compounds of formula III wherein p is 1, 2, 3 or 4, the compounds offormula IV wherein A′ represents —(CH₂)_(p-1)— and p is 3 or 4, thecompounds of formula VI wherein p is 1, 2, 3 or 4 and the compounds offormula XV wherein p is 1, 2, 3 or 4 can be obtained as described inScheme 2 hereafter.

In Scheme 2, PG⁴ represents —C(O)R^(g), wherein R^(g) represents alkyl,or PG⁴ represents a silyl protecting group such as TBDMS or TBDPS.

The alcohols of formula II-2 can be obtained by reaction of the epoxidesof formula II-1 with the anions of the carbamates of formula G-NH—COORwherein R represents alkyl or benzyl in presence of a base such as KHDMSor lithium tert-butylate, followed by alcohol deprotection as describedin general reaction technique 8. The compounds of formula III can thenbe obtained from the alcohols of formula II-2 using general reactiontechnique 3. The compounds of formula IV wherein A′ represents—(CH₂)_(p-1)— and p is 3 or 4 can be obtained by oxidation of thecorresponding alcohol derivatives of formula II-2 using general reactiontechnique 9. The compounds of formula VI can be obtained by reaction ofthe compounds of formula III with sodium azide and subsequenttransformation into the corresponding amine following general reactiontechnique 12. Finally, the compounds of formula XV are obtained byreaction of intermediates of formula VI with an aldehyde of formulaR³′CHO following general reaction technique 2 or with a derivative offormula R³′CH₂L⁴ wherein R³′ represents a silylether protected form ofthe group R³ and L⁴ represents a halogen such as iodine, bromine orchlorine or a group of the formula OSO₂R^(a) wherein R^(a) is alkyl, CF₃or tolyl following general reaction technique 1.

The compounds of formula IV wherein A′ is —CH₂CH(OPG)-, PG being a silylprotecting group such as TBDMS or TBDPS, are prepared as described inScheme 3 hereafter.

In Scheme 3, R^(h) represents alkyl (notably tBu) and PG represents analcohol protecting group such as TBDMS or TBDPS.

The compounds of formula III-1 can be reacted (Scheme 3) with the aminesof formula G-NH₂ followed by reaction with CDI, affording theoxazolidinones of formula III-2. The corresponding alcohol derivativesof formula III-3 can be obtained after reduction of the ester of formulaIII-2 using general reaction technique 5. The corresponding aldehydes offormula IV can then be obtained by oxidation of the alcohol derivativesof formula III-3 using general reaction technique 9.

The compounds of formula V wherein each of R⁴ and R⁵ represents H and nis 1 or 2 can be prepared as described in Scheme 4 hereafter.

In Scheme 4, R^(i) represents alkyl or benzyl and n is 1 or 2.

The esters of formula Iv-1 can be treated with paraformaldehyde in thepresence of a base such as TEA or K₂CO₃. The resulting alcohols offormula Iv-2 can be activated using general reaction technique 3 andcyclised under thermal conditions. The resulting esters of formula Iv-3can be reduced using general reaction technique 5, affording thealcohols of formula Iv-4, which can be activated using general reactiontechnique 3, affording the compounds of formula V wherein n is 1. Thecarbanions of the esters of formula IV-1, generated in the presence ofLDA in THF at −78° C., can also be treated with4-(iodomethyl)-2,2-dimethyl-1,3-dioxolane (commercial), affording theesters of formula IV-5, which can be further transformed into thecorresponding alcohols of formula IV-6 using general reaction technique5. These alcohols can be activated using general reaction technique 3and cyclised under thermal conditions, affording the tricyclicderivatives of formula IV-7. The acetonide protecting group can beremoved under acidic conditions such as aq. acetone in presence ofdiluted aq. HCl, or an acidic cation exchange resin such as Amberlite®IR120. The corresponding diols can be cleaved in presence of NaIO₄ toyield the corresponding aldehydes, which can be reduced into thecorresponding alcohols of formula IV-8 by treatment with a hydridereagent such as NaBH₄, followed by alcohol activation using generalreaction technique 3, affording the compounds of formula V wherein n is2. The compounds of formulae IV-3, IV-4, IV-7, IV-8 and V wherein“-----” is absent and U represents CH₂ or NH can be obtained byhydrogenation of the corresponding compounds of formulae IV-3, IV-4,IV-7, IV-8 and V wherein “-----” is a bond and U represents CH or N. Thecompounds of formulae IV-4, IV-7, IV-8 and V wherein “-----” is a bondand U represents N can also be reduced into the corresponding compoundswherein “-----” is absent and U represents NH using NaBH₄, whereby thetransformation of the compounds of formula IV-4 wherein U represents NHinto the corresponding compounds of formula V is then preferablyperformed after transient protection of the NH group.

The compounds of formula V wherein R⁴ represents OH can be prepared asdescribed in Scheme 4a hereafter.

The compounds of formula V wherein R⁴ is OH and n is 1 can be obtained(Scheme 4a) by transforming the compounds of formula IV-4 into thealkene derivatives of formula IVa-1 after activation of the alcoholgroup using general reaction technique 3 followed by treatment with abase such as DBU. The intermediate alkene derivatives of formula IVa-1can be dihydroxylated using general reaction technique 6 and the primaryalcohol function of the intermediates of formula Ib-1 can then beactivated using general reaction technique 3, affording the compounds offormula V wherein R⁴ is OH and n is 1. The compounds of formula Vwherein R⁴ is OH and n is 2 can be obtained by oxidizing the derivativesof formula Ib-1 using general reaction technique 9, performing a Wittigreaction with methoxymethylene triphenylphosphorane and an acidichydrolysis of the intermediate of formula IVa-3 and reducing thealdehyde thus obtained into the alcohol derivatives of formula Ib-2using general reaction technique 5 before activating the alcoholfunction using general reaction technique 3. The compounds of formulaIb-2 can also be obtained by reaction of the aldehydes of formula IVa-2with methylenetriphenylphosphorane followed by hydroboration of theintermediate vinyl derivatives of formula IVa-4 with a borane reagentsuch as 9-BBN, BH₃.Me₂S or BH₃.THF followed by oxidation with H₂O₂ inpresence of NaOH.

The compounds of formulae IVa-2 and V wherein “-----” is absent and Urepresents CH₂ or NH can be obtained by hydrogenation of thecorresponding compounds wherein “-----” is a bond and U represents CH orN.

The compounds of formula VII can be obtained by oxidation of thecorresponding alcohols of formulae Ib-1, Ib-2, IV-4 and IV-8 followinggeneral reaction technique 9.

The compounds of formula VIII wherein R²⁰ represents CH₂R³′, each of R⁴and R⁵ represents H and p is 1, 2 or 3 can be obtained as described inScheme 5 hereafter.

In Scheme 5, Hal represents halogen such as chlorine or bromine, R²⁰represents CH₂R³′ and R³′ represents hydrogen or (C₁-C₃)alkyl or alsoR³′ represents a (C₁-C₃)hydroxyalkyl group the hydroxy of which isprotected in the form of a silyl ether (e.g. as a TBDMS or TBDPS ether).

The amine derivatives of formula XIII wherein each of R⁴ and R⁵represents H can be reacted with the halogenides of formula V-1following general reaction technique 1. The resulting derivatives offormula V-2 can be dihydroxylated following general reaction technique6, the primary alcohol function can be activated following generalreaction technique 3 and the epoxide ring can then be formed aftertreatment with a base such as NaH, Na₂CO₃ or TEA. The epoxides offormula V-3 can then be treated with sodium azide followed by formationof the corresponding amines following general reaction technique 12 andsubsequently be converted into their corresponding carbamates with CbzClor Boc₂O following general reaction technique 10. The oxazolidinone ringcan then be formed by reaction with NaH. The compounds of formula VIIIcan also be obtained by reaction of the epoxide derivatives of formulaV-3 with a carbamic acid ester in the presence of a salen complex asdescribed in Org. Letters (2004), 6, 3973-3975 or Org. Letters (2005),7, 1983-1985). The compounds of formula VIII wherein U is CH₂ or NH and“-----” is absent, can be obtained by hydrogenation of the correspondingcompounds of formula VIII wherein “-----” is a bond and U represents CHor N. The compounds of formula VIII wherein “-----” is a bond and Urepresents N can also be reduced into the corresponding compoundswherein “-----” is absent and U represents NH using NaBH₄.

Certain compounds of formula IX are commercially available (e.g. G=G¹,Q=O and X=N: CAS 337463-99-7; G=G¹, Q=S and X=CH: CAS 6376-70-1; G=G¹,Q=O and X=CH: CAS 7652-29-1) or can be obtained according to knownliterature procedures (e.g. 7-chloro-1,8-naphthyridin-2(1R)-one: J. Org.Chem. (1990), 4744-59).

The compounds of formula IX wherein L³ is Cl, G is a group G¹, X is Nand Q is S can be obtained as described in Scheme 6 hereafter.

Accordingly, the bromo derivative of formula VI-1 (prepared according toWO 2008/065198) can be reacted with bromoacetyl bromide and theresulting derivative of formula VI-2 can be reacted with sodiumthioacetate in presence of NaOMe to afford the compound of formula IXwherein L³=Cl, G=G¹, X=N and Q=S.

The compounds of formula X wherein A′ represents —(CH₂)_(p)— arecompounds of formula I wherein R² represents H. The compounds of formulaX wherein A′ represents —CH₂CH₂CH(OPG)- can be obtained by reactingcompounds of formula II wherein n is 0 with compounds of formula IVwherein A′ represents —CH₂CH(OPG)- using general reaction technique 2.

The compounds of formula XI can be prepared by activation of thecorresponding commercially available alcohol derivatives (e.g.3-[(tert-butyldimethylsilyl)oxy]-1-propanol or2-tert-butyldimethylsilyloxyethanol) following general reactiontechnique 3.

The compounds of formula XII (e.g.(tert-butyldimethylsilyloxy)acetaldehyde or3-[(tert-butyldimethylsilyl)oxy]propionaldehyde) and XIIa arecommercially available.

The compounds of formula XIII wherein R³′ represent H or (C₁-C₃)alkyl oralso R³′ represents a (C₁-C₃)hydroxyalkyl group, the hydroxy of which isprotected in the form of a silyl ether (e.g. as a TBDMS or TBDPS ether),can be prepared by reductive amination of the aldehydes of formula XIIwith the amines of formula II following general reaction technique 2.These compounds of formula XIII can also be obtained by alkylation ofthe amines of formula II with the derivatives of formula XI followinggeneral reaction technique 1.

The compounds of formula XIV wherein A′ represents —(CH₂)_(p-1)— can beprepared by oxidation of the compounds of formula II-2 or IV followinggeneral reaction technique 14. The compounds of formula XIV wherein A′represents —CH₂CH(OPG)-, PG being a silyl protecting group such as TBDMSor TBDPS, can be prepared by hydrolysis of the corresponding esters offormula III-2 (see Scheme 3) using a base such as LiOH in the casewherein R^(h) is methyl or ethyl or TFA in the case wherein R^(h) istBu.

The compounds of formula XV wherein R³′ represents hydrogen or(C₁-C₃)alkyl or also R³′ represents a (C₁-C₃)hydroxyalkyl group, thehydroxy of which is protected in the form of a silyl ether (e.g. as aTBDMS or TBDPS ether), can be obtained by alkylation of the amines offormula VI with derivatives of formula R³′—CH₂—X (X being Cl, Br or I)following general reaction technique 1.

The compounds of formula XVI can be obtained from the correspondingcompounds of formula I wherein R⁵ represents (CH₂)_(z)OH followinggeneral reaction technique 3.

The compounds of formula XVII can be obtained as described in Scheme 6ahereafter.

In Scheme 6a, PG⁰ represents an amino protecting group such as Ac, Boc,Cbz or Fmoc and R⁹″ represents hydrogen or (C₁-C₂)alkyl or also R⁹″represents a (C₁-C₂)hydroxyalkyl group, the hydroxy of which isprotected in the form of a silyl ether (e.g. as a TBDMS or TBDPS ether).

The compounds of formula I_(6a) (i.e. the compounds of formula I wherein“-----” is a bond, R⁰ is H, U is N and R² is H) can be protected with anamino protecting group PG⁰ using general reaction technique 10. Theresulting compounds of formula 6a-1 can be transformed into thederivatives of formula 6a-2 by reduction over a noble metal catalystsuch as Pd/C or reduced with a hydride reagent such as NaBH₄. Theintermediates of formula 6a-2 can be reacted with the aldehydes offormula 6a-3 following general reaction technique 2, yielding thecompounds of formula XVII. Alternatively, the compounds of formula 6a-2can be transformed into the compounds of formula XVII by reaction withthe alkyl halogenides of formula R⁹′-Hal (Hal being a halogen atom).

Preparation of the Intermediates of Formulae I-1, Ia-1, Id-1, Id-6,Ie-1, II-1, III-1, IV-1 and XIII:

The compounds of formula I-1 can be obtained from the compounds offormula IV-1 as described in Scheme 7 hereafter.

In Scheme 7, R^(j) is alkyl or benzyl.

The esters of formula IV-1 can be reacted (Scheme 7) withbromoacetonitrile in the presence of a strong base such as LiHMDS in asolvent such as THF between −78° C. and −20° C. The resulting nitrilederivatives of formula VII-1 can be reduced with LAH in a solvent suchas THF or ether and the amino group of the resulting compounds offormula VII-2 can be protected according to general reaction technique10, affording compounds of formula I-1 wherein n is 2. The esters offormula IV-1 can also be reacted with N-(bromomethyl)phthalimide inpresence of a strong base such as LiHMDS in a solvent such as THFbetween −78° C. and −20° C. The resulting phthalimido derivatives offormula VII-3 can then be treated with an hydrazine derivative such ashydrazine hydrate, affording the corresponding primary amine derivativesof formula VII-4 wherein n is 1. The amino group of the derivatives offormula VII-4 can be protected according to general reaction technique10 and the ester function reduced using general reaction technique 5 toobtain the compounds of formula I-1 wherein n is 1. The esters offormula IV-1 can also be reacted with NBS, affording the correspondingbromides of formula VII-5 which can then be reacted with potassiumphthalimide. The resulting phthalimido derivatives of formula VII-6 canbe treated with an hydrazine derivative such as hydrazine hydrate toobtain the corresponding primary amine derivatives of formula VII-4wherein n is 0. The amino group of the derivatives of formula VII-4 canthen be protected according to general reaction technique 10 and theester function reduced using general reaction technique 5, affordingcompounds of formula I-1 wherein n is 0.

The compounds of formula I-1 wherein n is 0 can furthermore be obtainedfrom the compounds of formula III-2 as described in Scheme 7a hereafter.

In Scheme 7a, PG¹ represents an amino protecting group such as Boc orFmoc and PG⁵ represents an alcohol protecting group such as TBDMS orTBDPS.

The compounds of formula I-1 wherein n is 0 can also be obtained (Scheme7a) from the alkene derivatives of formula III-2. The primary alcoholfunction of the diols of formula III-2 can be protected using generalreaction technique 7 before conversion of the secondary alcohol groupinto the corresponding azide by activation of the alcohol underMitsunobu conditions (in the presence of PPh₃ and DEAD or DIAD in asolvent such as THF, DMF, DCM or DME between −20° C. and 60° C., asreviewed by O. Mitsunobu in Synthesis (1981), 1) reaction with DPPA,formation of the primary amine using general reaction technique 12 andformation of the carbamate using general reaction technique 10, toobtain the compounds of formula VIIa-1. The alcohol protecting group ofthe intermediates of formula VIIa-1 can then be removed using generalreaction technique 8.

The compounds of formula Ia-1 can be obtained from the aldehydes offormula VIII-2

by Wittig reaction with an alkoxycarbonylmethylene triphenylphosphorane.

The compounds of formula Id-1 can be prepared according to WO 02/08224,WO 2004/058144 or WO 2008/126024 or as described in Scheme 8 hereafter.

In Scheme 8, L⁵ represents halogen (such as bromine) or OTf.

The compounds of formula VIII-1 (see Scheme 8) can be reacted withtrivinylboroxin in presence of a palladium catalyst such astetrakis(triphenylphosphine)palladium, affording the compounds offormula Id-1 wherein R⁰ represents H. The compounds of formula Id-1(including those wherein R⁰ represents (C₁-C₃)alkoxy) can also beobtained by reacting the aldehydes of formula VIII-2 withmethylenetriphenylphosphorane.

The compounds of formula Id-6 can be obtained in analogy to thecompounds of formula Id-1 starting from the derivatives of formulaVIII-3

(commercially available or prepared according to WO 2008/148867, WO2008/003690, WO 2006/125974 or WO 2008/150827).

The compounds of formula Ie-1 can be obtained by protection of the aminogroup of the corresponding compounds of formula II wherein R¹ representshalogen using general reaction technique 10.

The compounds of formula II-1 wherein p is 1 and PG⁴ is —C(O)R^(g),R^(g) being alkyl, are commercially available. The compounds of formulaII-1 wherein p is 2 or 3 and PG⁴ is TBDMS can be prepared according toWO 2007/144423 or EP 518672.

The compounds of formula III-1 wherein PG is TBDMS can be preparedaccording or in analogy to Bioorganic & Medicinal Chemistry Letters(1996), 6(8), 991-994.

The compounds of formula IV-1 can be prepared as described in WO2007/122258, WO 2007/115947 and WO 2007/081597.

The compounds of formula VIII-1 wherein R¹ is H and L⁵ is OTf can beprepared according to WO 2004/002490. The compounds of formula VIII-1wherein R¹ is F can be prepared in analogy to the compounds of formulaVIII-1 wherein R¹ is Cl as described in WO 2006/021448.

The compounds of formula VIII-2 wherein R⁰ is H or methoxy, R¹ is H or Fand one of U and V is CH while the other is CH or N can be preparedaccording to WO 98/17672, WO 2006/046552, WO 2008/126024 or WO2008/152603.

The compounds of formula VIII-2 wherein U is N, V is N and R⁰ is H ormethoxy can be prepared as described in Scheme 9 hereafter.

In Scheme 9, X represents halogen such as bromine or chlorine.

The diamino derivatives of formula IX-1 can be reacted with bromoaceticacid, affording the intermediates of formula IX-2 which can then beoxidised using MnO₂. The aromatic intermediates of formula IX-3 can bereacted with methyl iodide in the presence of CsCO₃, affording thecompounds of formula IX-7 wherein R⁰ is H. The compounds of formula IX-7wherein R⁰ is OMe can be obtained by reacting the compounds of formulaIX-1 with diethyl glyoxylate, affording the intermediates of formulaIX-5 which can further be transformed into the derivatives of formulaIX-6 by reaction with POCl₃ and the derivatives of formula IX-7 whereinR⁰ is OMe after reaction with NaOMe in MeOH. The compounds of formulaIX-7 can then be transformed into the derivatives of formula VIII-2after reaction with a strong base such as n-BuLi and trapping thegenerated intermediates with DMF.

The compounds of formula IX-1 wherein R¹ is H can be prepared asdescribed in U.S. Pat. No. 5,298,518. The compound of formula IX-1wherein X is Br and R¹ is F can be obtained as summarised in Scheme 10hereafter.

The commercially available pyridine derivative of formula X-1 can betransformed into the corresponding aminopyridine derivative of formulaX-2 by reaction with POCl₃ followed by ammonia. The intermediate offormula X-2 can then be reacted with HNO₃/AcOH and further reduced (e.g.with Zn/HCl), thus affording the compound of formula IX-1 wherein X isBr and R¹ is F.

Particular embodiments of the invention are described in the followingExamples, which serve to illustrate the invention in more detail withoutlimiting its scope in any way.

EXAMPLES

All temperatures are stated in ° C. Compounds are characterized by¹H-NMR (300 MHz) (Varian Oxford); or by ¹H-NMR (400 MHz) (Bruker Advance400). Chemical shifts

are given in ppm relative to the solvent used; multiplicities:s=singlet, d=doublet, t=triplet, q=quadruplet, p=pentuplet, hex=hexet,hep=heptet, m=multiplet, br.=broad, coupling constants are given in Hz.Alternatively compounds are characterized by LC-MS (Sciex API 2000 withAgilent 1100 Binary Pump with DAD and ELSD or an Agilent quadrupole MS6140 with Agilent 1200 Binary Pump, DAD and ELSD); by TLC (TLC platesfrom Merck, Silica gel 60 F₂₅₄); or by melting point. Compounds arepurified by chromatography on Silica gel 60A. NH₄OH as used for CC is25% aq.

The HPLCs are done over a stationary phase such as a rapid resolutionZorbax SB C18 (1.8 μm) column, or a rapid resolution Zorbax Eclipse PlusC18 (1.8 μm) column. Typical HPLC conditions are a gradient of eluent A(water:MeCN 95:5 with 0.1% of formic acid, in presence or not of 5mmol/L ammonium formate) and eluent B (MeCN:water 95:5 with 0.1% offormic acid, in the presence or not of 5 mmol/L ammonium formate), at aflow rate of 0.8 to 5 mL/min. Racemates can be separated into theirenantiomers as described before. Preferred conditions of chiral HPLCare: ChiralPak AD (4.6×250 mm, 5 μm) column, using an isocratic mixture(e.g. at a ratio of 10/90) of eluent A (EtOH, in presence ofdiethylamine in an amount of eg. 0.1%) and eluent B (Hex), at rt, at aflow rate of e.g. 0.8 mL/min.

General Procedures:

Procedure A: LAH Reduction of Esters:

To a solution of ester (1 mmol) in THF (15 mL), cooled to −10° C., isadded in one portion LAH (3.5 eq.). The mixture is stirred at the sametemperature for 0.5 h, then at 0° C./rt until completion of the reaction(1-3 h). Water (0.4 mL) is carefully added, followed by 2M NaOH (0.8 mL)and water (0.4 mL). After stirring for 5 min, Na₂SO₄ (1 g) is added andthe mixture is stirred for 15 min. The solids are filtered off andthoroughly washed with EA. The filtrate is concentrated under reducedpressure.

Procedure B: Boc Deprotection:

The Boc protected amine (1 mmol) is dissolved in DCM (5 mL) and treatedwith Et₃SiH (optional; 0.2 mL, 1.1 eq.) and TFA (2 mL). The mixture isstirred at rt for 1 h, concentrated in vacuo and taken up in DCM/aq.NH₄OH. The org. layer is washed with water, dried over MgSO₄ andconcentrated under reduced pressure.

Procedure C: Alkylation of Amines with Mesylates:

A solution of amine (1.0-2.3 mmol), mesylate (1 mmol) and DIPEA (1.1mmol) in dry DMSO is heated to 70° C. until completion of the reaction(1-5 days). After cooling, water and EA are added and the phases areseparated. The aq. layer is extracted two more times with EA and thecombined org. layers are washed with water (3×) and brine, dried overMgSO₄ and concentrated under reduced pressure. The residue is thenpurified by CC.

Procedure D: Alkylation of Amines with Iodides:

A solution of amine (1 mmol), iodide (1 mmol) and DIPEA (1.1 mmol) indry DMSO is heated to 70° C. until completion of the reaction (1-3days). After cooling, water and EA are added and the phases areseparated. The aq. layer is extracted two more times with EA and thecombined org. layers are washed with water (3×) and brine, dried overMgSO₄ and concentrated under reduced pressure. The residue is thenpurified by CC.

Procedure E: Reductive Amination:

A solution of amine (1 mmol) and aldehyde (1 mmol) in DCE/MeOH (1-1 to4-1, 10 mL) is treated with NaBH(OAc)₃ (2 mmol). The mixture is stirredat rt until completion of the reaction (1-4 h), diluted with DCM andtreated with aq. NH₄OH. The phases are separated. The aq. layer isextracted two more times with DCM and the combined org. layers arewashed with water and brine, dried over MgSO₄ and concentrated underreduced pressure. The residue is then purified by CC.

Procedure F: Hydrogenation:

A solution of unsaturated substrate (1 mmol) in MeOH (20 mL) and AcOH(optional, 20 mL) is hydrogenated over 10% Pd/C (200 mg) for 20 h. Thecatalyst is filtered off, washed with MeOH/DCM and concentrated. Waterand 28% aq. NH₄OH are added and the mixture is extracted with DCM/MeOH9:1. The org. layer is dried over MgSO₄, concentrated and purified byCC.

Procedure G: Boc Protection:

Boc₂O (1.05 eq.) and TEA (1.5 eq.) are added at rt to a solution of thecorresponding amine (1.0 eq.) in THF. The reaction mixture is stirred atrt for 1 h, concentrated to dryness and purified by CC.

Procedure H: Mesylate Formation:

TEA or DIPEA (2 eq.) and MsCl (1.2 eq.) are added at 0° C. to a solutionof the required alcohol (1 eq.) in DCM or DCE. The reaction is stirred 1h at this temperature. In the case the resulting mesylate can undergocyclization to form a tricyclic system, the reaction mixture is furtherstirred between rt and 45° C. for 6 to 72 h. Sat. aq. NaHCO₃ is thenadded and the mixture is extracted with DCM (3×). The combined org.layers are dried over MgSO₄, filtered and concentrated under reducedpressure to afford the desired mesylate which can be used as such in afurther step.

Procedure I: Oxazolidinone Formation with CDI:

A solution of the required aminoalcohol (1 eq.) in THF is treated withCDI (1.5 eq.) and heated at 50° C. overnight. The mixture is cooled tort, diluted with EA and washed with water. The org. layer is washed with0.5M HCl (optionally) and water, dried over MgSO₄ and concentrated. Theresidue is either triturated with an org. solvent, crystallized fromHept/EA or purified by CC.

Procedure J: Deprotection of TBDMS Ethers:

A solution of TBDMS ether (1 eq) in THF is treated with TBAF (1Msolution in THF, 1.2 eq.) at 0° C. The solution is stirred at 0° C. for6 h. The mixture is partitioned between water and EA and the aq. phaseis extracted with EA (3×). The combined org. layers are washed withwater (3×) and brine, dried over MgSO₄ and concentrated under reducedpressure. The residue is triturated with an org. solvent or purified byCC.

Procedure K: Finkelstein-Like Iodide Formation:

A suspension of the mesylate (1 eq.) and NaI (3 eq.) in 2-butanone isheated at 85° C. between 3 h and 3 days. After cooling, the mixture isdiluted with ether/EA and treated with 10% aq. Na₂S₂O₃. After stirringfor 10 min, the phases are separated and the aq. layer was washed withEA. The combined org. layers are washed with water (2×), dried overMgSO₄ and concentrated under reduced pressure. The residue is trituratedwith an org. solvent.

Procedure L: Asymmetric Dihydroxylation (Chem. Rev. (1994), 94, 2483):

A mixture of olefin (1 mmol) in t-BuOH/H₂O (1:1, 10 mL) at rt is treatedwith methylsulfonamide (1 eq.) and AD-mix α or β (1.5 g). The mixture isvigorously stirred at rt until completion of reaction, Na₂S₂O₃ (1.5 g)is added and the mixture diluted with EA (30 mL). The phases areseparated and the aq. phase is extracted once more with EA. The combinedorg. layers are washed with water and brine, dried over MgSO₄ andconcentrated. The residue is purified by CC.

Procedure M: TBDMS Protection:

A solution of alcohol (1 eq.) and imidazole (1.1 eq.) in THF (10mL/mmol) at 0° C. is treated dropwise with a solution of TBDMSCl (1 eq.)in THF. The mixture is stirred at rt until complete conversion. Themixture is diluted with EA, washed with water and brine, dried overMgSO₄ and concentrated. The residue is purified by CC.

Procedure N: Mitsunobu Reaction:

To a solution of alcohol (1 eq.) and PPh₃ (1.1 eq.) in THF (2 ml/mmol)cooled to 0° C., DPPA (1.1 eq.) and DIAD (1.2 eq.) are added dropwiseand the mixture warmed to rt over 1 h and stirred at this temperatureuntil completion of reaction. The mixture is concentrated under reducedpressure and the residue purified by CC.

Procedure N′: Mitsunobu Reaction with Staudinger Conditions and BocProtection:

After performing procedure N with the alcohol (1 eq.) as previouslydescribed, the azide is dissolved in THF/water (9:1) and treated withPPh₃ (1.2 eq.) and the resulting solution heated at 50° C. untilcomplete conversion to the amine. The mixture is cooled an treated withBoc₂O (1.5 eq) and stirred at rt overnight. The volatiles are removedunder reduced pressure and the residue purified by CC to give theBoc-protected amine.

Preparation A:rac-1-aminomethyl-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-oneA.i. (7-fluoro-2-methoxy-quinolin-8-yl)-acetonitrile

To a solution of 8-bromomethyl-7-fluoro-2-methoxy-quinoline (20.0 g, 74mmol; prepared as in WO 2007/081597) in DMF (530 mL) was added KCN (22.1g, 339 mmol) and the mixture was stirred at 70° C. overnight. Themixture was concentrated, water and EA were added and the aq. layer wasextracted with EA. The combined org layers were washed with brine, driedover MgSO₄ and concentrated to afford the title intermediate as a beigesolid (16.13 g, 100% yield).

MS (ESI, m/z): 217.4 [M+H⁺].

A.ii. (7-fluoro-2-methoxy-quinolin-8-yl)-acetic acid methyl ester

To a solution of intermediate A.i (16.1 g, 75 mmol) in MeOH (270 mL) wasadded TMSCl (32 mL, 3.38 eq) and the solution was stirred at 80° C. for3 h. The mixture was concentrated under reduced pressure and partitionedbetween EA and water. The phases were separated and the aq. layer wasextracted with EA. The combined org. layers were washed with 2MNaOH,water and brine, dried over MgSO₄, concentrated and purified by CC (DCM)to afford the title intermediate as a colourless solid (8.13 g, 44%yield).

MS (ESI, m/z): 250.2 [M+H⁺].

A.iii.rac-3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-2-(7-fluoro-2-methoxy-quinolin-8-yl)-propionicacid methyl ester

To a solution of LiHMDS (31.3 mL, 1M in THF) in THF (40 mL) was added at−78° C. a solution of intermediate Ali (6.50 g, 26 mmol) in THF (50 mL)over 10 min. After stirring for 1 h at −78° C., a solution ofN-(bromomethyl)phthalimide in THF (50 mL) was added dropwise over 10min. The mixture was stirred at −78° C. for 1 h and then at rtovernight. The resulting solution was quenched with 1N HCl (260 mL) andextracted with DCM. The combined org. layers were washed with water,dried over MgSO₄, concentrated and purified by CC (Hept/EA 1:1). Theresulting solid was triturated with EA to afford the title intermediateas a colourless solid (2.42 g, 23% yield).

MS (ESI, m/z): 409.3 [M+H⁺].

A.iv. rac-3-amino-2-(7-fluoro-2-methoxy-quinolin-8-yl)-propionic acidmethyl ester

To a suspension of intermediate A.iii (2.40 g, 5.88 mmol) in EtOH (40mL) was added dropwise hydrazine monohydrate (1.43 mL, 5 eq.) at rt. Themixture was stirred for 2 h at rt and then concentrated. The residue wastaken up in EA and 10% citric acid and the layers were separated. Theaq. phase was treated another time with EA. The aq. phase was basifiedwith NH₄OH and extracted twice with DCM. The combined DCM phases weredried over MgSO₄ and concentrated to afford the title intermediate as apale yellow oil (1.62 g, 99% yield).

MS (ESI, m/z): 279.4 [M+H⁺].

A.v.rac-3-tert-butoxycarbonylamino-2-(7-fluoro-2-methoxy-quinolin-8-yl)-propionicacid methyl ester

Starting from intermediate A.iv (1.62 g, 5.82 mmol) and using procedureG, the title intermediate was obtained as a colourless solid (1.87 g,85% yield).

MS (ESI, m/z): 379.2 [M+H⁺].

A.vi.rac-[2-(7-fluoro-2-methoxy-quinolin-8-yl)-3-hydroxy-propyl]-carbamicacid tert-butyl ester

Starting from intermediate A.v and using procedure A, the titleintermediate was obtained as a colourless solid (1.69 g, 98% yield).

MS (ESI, m/z): 351.3 [M+H⁺].

A.vii.rac-(9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-ylmethyl)-carbamicacid tert-butyl ester

Starting from intermediate A.vi (1.68 g, 4.8 mmol) and using procedureH, the title intermediate was obtained as a beige solid (1.56 g, 100%yield).

MS (ESI, m/z): 319.3 [M+H⁺].

A.viii.rac-1-aminomethyl-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from intermediate A.vii and using procedure B, the titlecompound was obtained as a pale orange solid (1.08 g, quant.).

¹H NMR (CDCl₃) δ: 7.66 (d, J=9.4 Hz, 1H), 7.40 (dd, J=8.8, 4.7 Hz, 1H),6.88 (m, 1H), 6.61 (d, J=9.4 Hz, 1H), 4.53 (dd, J=12.9, 9.4 Hz, 1H),4.36 (dd, J=12.9, 4.7 Hz, 1H), 3.95 (m, 1H), 1.97 (m, 2H), 3.15 (m, 2H).

MS (ESI, m/z): 219.2 [M+H⁺].

Preparation B:rac-1-(2-amino-ethyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-oneB.i. rac-3-cyano-2-(7-fluoro-2-methoxy-quinolin-8-yl)-propionic acidmethyl ester

LiHMDS (18.4 mL, 1.1 eq., 1M in THF) was added at −78° C. within 15 minto a solution of intermediate A.ii (4.17 g, 16.7 mmol) in THF (40 mL).The resulting mixture was stirred at −78° C. for 2 h. Bromoacetonitrile(3.0 g, 1.5 eq.) was added within 20 min and stirring was continued at−78° C. for 2 h. The reaction was quenched with water and extracted withEA (3×). The combined org. phases were washed with brine, dried overMgSO₄, filtered and concentrated. The residue was purified by CC(Hept/EA 2:1 to 1:1) to afford the title intermediate as a yellow solid(3.96 g, 82% yield).

MS (ESI, m/z): 289.4 [M+H⁺].

B.ii. rac-4-amino-2-(7-fluoro-2-methoxy-quinolin-8-yl)-butan-1-ol

To a solution of AlCl₃ (4.0 g, 30 mmol) in ether (150 mL) were added LAH(30 mL, 1M in THF) dropwise within 10 min at −78° C. After stirring for15 min, a suspension of intermediate B.i (3.94 g, 13.7 mmol) in ether(120 mL) was added within 15 min. The suspension was then stirred at rtfor 4 h, cooled to 0° C., quenched with sat. aq. Na₂SO₄. The mixture wasbasified with NH₄OH and extracted with EA (3×). The combined org. phaseswere dried over Na₂SO₄, filtered and concentrated to afford the titleintermediate as a yellow oil (3.86 g, quant.) which was used as such inthe next step.

MS (ESI, m/z): 265.4 [M+H⁺].

B.iii.rac-[3-(7-fluoro-2-methoxy-quinolin-8-yl)-4-hydroxy-butyl]-carbamic acidtert-butyl ester

Starting from intermediate B.ii (3.85 g, 14.57 mmol) and using procedureG, the title intermediate was obtained as a yellow oil (2.69 g, 51%yield).

MS (ESI, m/z): 365.1 [M+H⁺].

B.iv.rac-[2-(9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-ethyl]-carbamicacid tert-butyl ester

Starting from intermediate B.iii (2.68 g, 7.4 mmol) and using procedureH, the title intermediate was obtained as a pale orange solid (2.67 g,quant.) which was used as such in the next step.

MS (ESI, m/z): 333.1 [M+H⁺].

B.v.rac-1-(2-amino-ethyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from intermediate B.iv and using procedure B, the titlecompound was obtained after CC (DCM/MeOH/NH₄OH 1000:50:4) as a paleorange solid (1.34 g, 72% yield).

¹H NMR (CDCl₃) δ: 7.68 (d, J=9.3 Hz, 1H), 7.40 (dd, J=8.8, 4.8 Hz, 1H),6.89 (m, 1H), 6.63 (d, J=9.5 Hz, 1H), 4.56 (dd, J=12.8, 9.3 Hz, 1H),4.21 (dd, J=12.5, 4.8 Hz, 1H), 4.00 (m, 1H), 2.89 (m, 2H), 2.18 (m, 1H),1.86 (m, 1H), 1.24 (m, 2H).

MS (ESI, m/z): 233.5 [M+H⁺].

Preparation C:rac-1-amino-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one C.i.rac-bromo-(7-fluoro-2-methoxy-quinolin-8-yl)-acetic acid methyl ester

NBS (1.6 g) and AIBN (0.1 g) were added to a mixture of intermediateA.ii (1.50 g, 6.0 mmol) in trifluorotoluene (30 mL). The mixture washeated at 80° C. under a sunlamp beam for 5 h. After cooling, thereaction mixture was concentrated. The residue was taken in EA andwashed twice with 10% sodium thiosulfate, dried over Na₂SO₄, filteredand concentrated to dryness. The residue was triturated with Hept/EA toafford the title intermediate as a colourless solid (1.42 g, 72% yield).

MS (ESI, m/z): 328.2 [M+H⁺].

C.ii.rac-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-(7-fluoro-2-methoxy-quinolin-8-yl)-aceticacid methyl ester

To a solution of intermediate C.i (1.31 g, 4.0 mmol) in dry DMF (25 mL)was added potassium phthalimide (1.24 g, 6.6 mmol) under Ar. Theresulting solution was stirred at 120° C. for 1 h. After cooling to rt,water was added and the mixture was extracted with EA. The org. layerwas washed with water and brine, dried over MgSO₄ and concentrated. Theresidue was crystallized from Hept/EA to afford the title intermediateas a beige solid (1.04 g, 66% yield).

MS (ESI, m/z): 395.1 [M+H⁺].

C.iii. rac-amino-(7-fluoro-2-methoxy-quinolin-8-yl)-acetic acid methylester

To a solution of intermediate C.ii (714 mg, 1.81 mmol) in EtOH (10 mL)was added dropwise hydrazine monohydrate (0.9 mL, 10 eq.) at rt. Themixture was stirred for 3 h at rt, after which a precipitate had formed,which was filtered off. The filtrate was concentrated under reducedpressure and partitioned between EA and 10% citric acid. The aq. layerwas washed once more with EA and then basified using NH₄OH. The aq.layer was extracted with DCM and the org. layer was concentrated underreduced pressure to afford the title intermediate as a colourless solid(398 mg, 83% yield).

MS (ESI, m/z): 265.5 [M+H⁺].

C.iv.rac-tert-butoxycarbonylamino-(7-fluoro-2-methoxy-quinolin-8-yl)-aceticacid methyl ester

Starting from intermediate C.iii (380 mg, 1.44 mmol) and using procedureG, the title intermediate was obtained as a colourless solid (560 mg,100% yield).

MS (ESI, m/z): 365.0 [M+H⁺].

C.v. rac-[7-(7-fluoro-2-methoxy-quinolin-8-yl)-2-hydroxy-ethyl]-carbamicacid tert-butyl ester

Starting from intermediate C. iv and using procedure A, the titleintermediate was obtained as a pale yellow solid (473 mg, 92% yield).

MS (ESI, m/z): 337.3 [M+H⁺].

C.vi.rac-(9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamicacid tert-butyl ester

TEA (0.4 mL, 2 eq.) and MsCl (0.13 mL, 1.2 eq.) were added at 0° C. to asolution of intermediate C.v (470 mg, 1.40 mmol) in DCM (10 mL). Thereaction proceeded for 20 min at this temperature. Sodium bicarbonateand DCM were added. The two layers were decanted and the aq. layer wasextracted once more with DCM. The combined org. layers were dried overNa₂SO₄, filtered and concentrated to dryness. The residue was carried onwithout further purification. A solution of the crude mesylate intoluene (20 mL) was heated at 85° C. overnight. After cooling to rt,water and EA were added and the layers separated. The aq. layer wasextracted once more with EA and the combined org. layers were washedwith saturated NaHCO₃ and concentrated. The residue was triturated withether/EA to afford the title intermediate as a colourless solid (193 mg,45% yield).

MS (ESI, m/z): 305.0 [M+H⁺].

C.vii. rac-1-amino-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from intermediate C.vi and using procedure B, the titlecompound was obtained as a beige solid (128 mg, 100% yield).

¹H NMR (DMSO-d₆) δ: 7.88 (d, J=9.4 Hz, 1H), 7.61 (dd, J=8.5, 5.0 Hz,1H), 6.99 (dd, J=9.7, 8.8 Hz, 1H), 6.49 (d, J=9.4 Hz, 1H), 4.92 (dd,J=8.8, 4.4 Hz, 1H), 4.44 (dd, J=12.9, 8.8 Hz, 1H), 3.86 (dd, J=12.6, 3.8Hz, 1H), 2.29 (s, 2H).

MS (ESI, m/z): 205.1 [M+H⁺].

Preparation D:(R)-4-amino-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one D.i.(R)-2-azido-2-(6-methoxy-[1,5]naphthyridin-4-yl)-ethanol and(S)-2-azido-1-(6-methoxy-[1,5]naphthyridin-4-yl)-ethanol

A mixture of (S)-2-methoxy-8-oxiranyl-[1,5]naphthyridine (4 g, 20 mmol;prepared as in WO 2006/002047), NH₄Cl (2.7 g, 2.5 eq) and NaN₃ (3.2 g,2.5 eq.) in MeOH (100 mL) and water (2 mL) was heated at 65° C. for 4 h,filtered and concentrated in vacuo. The residue was taken up in EA andwashed with sat. NaHCO₃ and brine, dried over MgSO₄ and concentrated.The residue was purified by CC (Hept/EA 1:1, 1:2, EA) to give a 3:2mixture of regioisomers (5 g, 100% yield) which was used as such in thenext step.

D.ii.[(R)-2-hydroxy-1-(6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]-carbamic acidtert-butyl ester

A solution of intermediate D.i (mixture of isomers, 5 g, 20.7 mmol) inTHF/MeOH 1:1 (200 mL) was hydrogenated over Pd/C (10%, 2.2 g) and 1 barof H₂ for 1 h. The catalyst was filtered off and the filtrateconcentrated under reduced pressure. The residue was dissolved in DCM(150 mL) and Boc₂O (6.8 g, 1.5 eq.) was added. The mixture was stirredat rt for 2 h, concentrated in vacuo and purified by CC (EA/Hept 2:1,EA, EA/MeOH 9:1) to give the more polar, desired isomer as a colourlessfoam (2.8 g, 43% yield).

¹H NMR (DMSO-d₆) δ: 8.72 (d, J=4.4 Hz, 1H), 8.24 (d, J=9.1 Hz, 1H), 7.56(d, J=4.4 Hz, 1H), 7.33 (d, J=8.5 Hz, 1H), 7.25 (d, J=9.1 Hz, 1H), 5.64(m, 1H), 3.99 (m, 3H), 3.78 (m, 1H), 3.58 (dd, J=10.8, 7.0 Hz, 1H), 1.35(s, 9H).

D.iii.((R)-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de][1,5]naphthyridin-4-yl)-carbamicacid tert-butyl ester

Starting from intermediate D.ii (2.8 g, 8.8 mmol) and using procedure H,the title intermediate was obtained as an off-white solid (1.2 g, 47%yield) after CC (EA, EA/MeOH 9:1) and crystallisation from ether/EA.

MS (ESI, m/z): 288.4 [M+H⁺].

D.iv. (R)-4-amino-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

A solution of intermediate D.iii (1 g, 3.48 mmol) in dioxane was treatedwith 4N HCl in dioxane (4 mL). The beige suspension was stirred at rtovernight, filtered and washed with ether and dried to give thedihydrochloride (475 mg, 52% yield). The free base was generated withthe use of ion exchange resin (Dowex 50), eluting with methanolicammonia to give a beige solid (0.3 g).

¹H NMR (DMSO-d₆) δ: 8.55 (d, J=4.7 Hz, 1H), 7.99 (d, J=9.7 Hz, 1H), 7.65(dd, J=4.7, 0.9 Hz, 1H), 6.82 (d, J=9.7 Hz, 2H), 5.12 (ddd, J=8.8, 4.1,0.9 Hz, 1H), 4.53 (dd, J=13.2, 8.8 Hz, 1H), 4.05 (m, 3H).

Preparation E:rac-4-aminomethyl-3-fluoro-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-oneE.i. 2-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-malonic acid diethylester

Diethyl malonate (12.4 mL, 81.7 mmol) was added to a suspension of NaH(3.0 g, 47.9 mmol, 60% in mineral oil) in dioxane (35 mL). The mixturewas stirred at rt for 5 min and then heated at 80° C. for 1 h. Aftercooling to rt, CuBr (1.4 g, 9.6 mmol) and8-bromo-7-fluoro-2-methoxy-[1,5]naphthyridine (7.0 g, 27.2 mmol,prepared according to WO 2007/122258) were added. The mixture wasstirred at 100° C. for 6 h. After cooling to rt, 10% NaHSO₄ (100 mL) wasadded. The mixture was stirred for 30 min at rt. The two layers weredecanted and the aq. layer was extracted three times with EA (3×150 mL).The combined org. layers were washed with brine, dried over Na₂SO₄,filtered and concentrated to dryness. The residue was purified by CC(Hept-EA 3:1 then 1:1) to afford the title intermediate as a yellow oil(8.22 g, 90% yield).

MS (ESI, m/z): 337.3 [M+H⁺].

E.ii. (3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-acetic acid ethylester

Water (0.53 mL, 1.2 eq.) and LiCl (2.07 g, 2 eq.) were added to asolution of intermediate E.i (8.22 g, 24.4 mmol) in DMSO (170 mL). Themixture was heated to 110° C. for 16 h and another 2.34 g of LiCl wereadded. The mixture was further heated at 110° C. for 16 h. The solventwas then evaporated under reduced pressure (bath temperature=70° C.,p=0.5 mbar). The residue was partitioned between 10% NaHSO₄ (200 mL) andether (200 mL). The aq. layer was extracted with ether (2×200 mL). Thecombined org. layers were filtered through a pad of silica gel. Thefiltrate was concentrated to dryness to afford the title intermediate asa brown oil (5.62 g, 87% yield).

MS (ESI, m/z): 265.3 [M+H⁺].

E.iii.rac-3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-2-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-propionicacid ethyl ester

To a solution of LiHMDS (4.54 mL, 1M in THF) in THF (11 mL) was added at−78° C. a solution of intermediate E.ii (1.0 g, 3.78 mmol) in THF (3 mL)over 10 min. After stirring for 1 h at −78° C. a solution ofN-(bromomethyl)phthalimide (1.09 g, 1.2 eq.) in THF (4 mL) was addeddropwise over 10 min. The mixture was stirred at −78° C. for 1 h andthen at rt overnight. The resulting solution was quenched with 1N HCland extracted with DCM. The combined org. layers were washed with water,dried over MgSO₄, concentrated and purified by CC (Hept/EA 1:1) toafford the title intermediate as an off-white solid (0.361 g, 43%yield).

MS (ESI, m/z): 424.4 [M+H⁺].

E.iv.rac-3-amino-2-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-propionic acidethyl ester

To a suspension of intermediate E.iii (368 mg, 0.87 mmol) in EtOH (6 mL)was added dropwise hydrazine monohydrate (0.21 mL, 5 eq.) at rt. Themixture was stirred for 2 h at rt and then concentrated. The residue wastaken up in EA and 10% citric acid and the layers were separated. Theaq. phase was treated another time with EA. The aq. phase was basifiedwith NH₄OH and extracted twice with DCM. The combined DCM phases weredried over MgSO₄ and concentrated to afford the title intermediate as ayellow oil (0.21 g, 82% yield).

MS (ESI, m/z): 203.0 [M+H⁺].

E.v.rac-3-tert-butoxycarbonylamino-2-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-propionicacid ethyl ester

Starting from intermediate E.iv (0.21 g, 0.72 mmol) and using procedureG, the title intermediate was obtained as a pale yellow foam (0.23 g,83% yield).

MS (ESI, m/z): 394.2 [M+H⁺].

E.vi.rac-[2-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-3-hydroxy-propyl]-carbamicacid tert-butyl ester

Starting from intermediate E.v (0.225 g, 0.57 mmol) and using procedureA, the title intermediate was obtained as a yellow foam (0.20 g, 100%yield).

MS (ESI, m/z): 202.2 [M+H⁺].

E.vii.rac-(3-fluoro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de][1,5]naphthyridin-4-ylmethyl)-carbamicacid tert-butyl ester

Starting from intermediate E.vi (0.20 g, 0.57 mmol) and using procedureH, the title intermediate was obtained as a beige solid (0.204 g,quant.) which was used as such in the next step.

MS (ESI, m/z): 320.2 [M+H⁺].

E.viii.rac-4-aminomethyl-3-fluoro-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from intermediate E.vii and using procedure B, the titlecompound was obtained as a brown oil (17 mg, 13% yield).

MS (ESI, m/z): 220.3 [M+H⁺].

Preparation F:rac-4-(2-amino-ethyl)-3-fluoro-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-oneF.i. rac-3-cyano-2-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-propionicacid ethyl ester

LiHMDS (4.2 mL, 1.1 eq., 1M in THF) was added at −78° C. within 15 minto a solution of intermediate E.ii (1.5 g, 5.68 mmol) in THF (15 mL).The resulting mixture was stirred at −78° C. for 2 h. Thenbromoacetonitrile (1.02 g, 1.5 eq.) was added within 20 min and stirringwas continued at −78° C. for 2 h. The reaction was quenched with waterand extracted with EA (3×). The combined org. phases were washed withbrine, dried over MgSO₄, filtered and concentrated. The residue waspurified by CC (Hept/EA 1:1) to afford the title intermediate as ayellow oil (1.30 g, 76% yield).

MS (ESI, m/z): 304.2 [M+H⁺].

F.ii.rac-4-amino-2-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-butan-1-ol

To a solution of AlCl₃ (1.3 g, 9.9 mmol) in ether (60 mL) were added LAH(9.9 mL, 1M in THF) dropwise within 10 min at −78° C. After stirring for15 min a suspension of intermediate F.i (1.36 g, 4.50 mmol) in ether (50mL) was added within 15 min. The suspension was then stirred for 1 h at−78° C. and for 1 h at −30° C. The mixture was then stirred for 2 h at0° C., quenched with sat. aq. Na₂SO₄. The mixture was basified withNH₄OH and extracted with EA (3×). The combined org. phases were driedover Na₂SO₄, filtered and concentrated. The residue was purified by CC(DCM/MeOH/NH₄OH 1000:100:8) to afford the title intermediate as a yellowoil (0.30 g, 25% yield).

MS (ESI, m/z): 266.3 [M+H⁺].

F.iii.rac-[3-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-4-hydroxy-butyl]-carbamicacid tert-butyl ester

Starting from intermediate F.ii (424 mg, 1.60 mmol) and using procedureG, the title intermediate was obtained as a a yellow solid (360 mg, 62%yield).

MS (ESI, m/z): 366.2 [M+H⁺].

F.iv.rac-[2-(3-fluoro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de][1,5]naphthyridin-4-yl)-ethyl]-carbamicacid tert-butyl ester

Starting from intermediate F.iii (360 mg, 0.99 mmol) and using procedureH, the title intermediate was obtained as a brown solid (360 mg, quant.)which was used as such in the next step.

MS (ESI, m/z): 334.1 [M+H⁺].

F.v.rac-4-(2-amino-ethyl)-3-fluoro-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from intermediate F.iv and using procedure B, the titlecompound was obtained after CC (DCM/MeOH/NH₄OH 1000:100:8) as a yellowsolid (130 mg, 49% yield).

MS (ESI, m/z): 234.3 [M+H⁺].

Preparation G: rac-6-amino-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-oneG.i. rac-2-azido-2-(3-methoxy-quinoxalin-5-yl)-ethanol

A mixture of 2-methoxy-8-oxiranyl-quinoxaline (4.7 g, 23 mmol; preparedas in WO 2004/002490), NH₄Cl (2.2 g, 1.8 eq.) and NaN₃ (3.8 g, 2.5 eq.)in MeOH (60 mL) was heated at 65° C. for 5 h, filtered and concentratedin vacuo. The residue was taken up in EA and washed with sat. NaHCO₃ andbrine, dried over MgSO₄ and concentrated. The residue was purified by CC(Hept/EA 1:1) to give the desired intermediate as a beige solid (4.4 g,77% yield).

¹H NMR (CDCl₃) δ: 8.52 (s, 1H), 8.02 (dd, J=8.5, 1.5 Hz, 1H), 7.77 (dd,J=7.3, 1.5 Hz, 1H), 7.60 (m, 1H), 5.90 (dd, J=7.6, 4.1 Hz, 1H), 4.13 (s,3H), 4.01 (dd, J=11.4, 3.8 Hz, 1H), 3.87 (dd, J=11.4, 7.9 Hz, 1H).

G.ii. rac-[2-hydroxy-1-(3-methoxy-quinoxalin-5-yl)-ethyl]-carbamic acidtert-butyl ester

A solution of intermediate G.i (4.48 g, 18.2 mmol) in THF (100 mL) andwater (3.2 mL) was treated with PPh₃ (5.3 g, 1.1 eq) and heated at 50°C. for 2 h. The mixture was concentrated to dryness and redissolved inether/EA. The org. phase was extracted twice with 1M HCl. The organicphase was discarded and the aqueous phase basified with 6N NaOH andextracted with DCM, dried over MgSO₄ and concentrated. The residue wasdissolved in DCM (150 mL) and treated with Boc₂O (4.8 g, 1.2 eq.). Themixture was stirred at rt for 1 h, concentrated in vacuo and purified byCC (EA/Hept 2:1, EA) to give the desired intermediate as a colourlessfoam (4.9 g, 84% yield).

¹H NMR (DMSO-d₆) δ: 8.60 (s, 1H), 7.87 (dd, J=8.2, 1.5 Hz, 1H), 7.70 (m,1H), 7.58 (m, 1H), 7.26 (m, 1H), 5.64 (td, J=7.6, 4.1 Hz, 1H), 4.76 (t,J=5.9 Hz, 1H), 4.06 (s, 3H), 3.71 (m, 1H), 3.54 (m, 1H), 1.35 (s, 11H).

G.iii.rac-(3-oxo-5,6-dihydro-3H-pyrrolo[1,2,3-de]quinoxalin-6-yl)-carbamicacid tert-butyl ester

Starting from intermediate G.ii (4.47 g, 14 mmol) and followingprocedure H, the reaction mixture was refluxed in DCE (100 mL) for 3days. The mixture was cooled to rt, diluted with DCM, washed with water,dried over MgSO₄ and concentrated. The residue was crystallized fromether/EA to give a mixture of the desired intermediate and thecorresponding oxazolidinone as an off-white solid (2.2 g) which was usedin the next step without further purification or characterization.

G.iv. rac-6-amino-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

A solution of intermediate G.iii (2.17 g, 3.8 mmol) in DCM (10 mL) wastreated with TFA (5 mL). The mixture was stirred at rt for 1 h,concentrated in vacuo and partitioned between DCM and water. The org.phase containing impurities was discarded and the aq. phase basifiedwith NH₄OH and extracted several times with DCM/MeOH 9:1. The combinedorg. phases were dried over MgSO₄ and concentrated to give the desiredcompound as an orange solid (0.36 g, 51% yield).

¹H NMR (DMSO-d₆) δ: 8.17 (s, 1H), 7.67 (d, J=8.2 Hz, 1H), 7.58 (dt,J=7.3, 0.9 Hz, 1H), 7.32 (dd, J=7.9, 7.3 Hz, 1H), 4.77 (dd, J=8.5, 4.4Hz, 1H), 4.50 (dd, J=13.2, 8.5 Hz, 1H), 3.86 (dd, J=13.2, 4.4 Hz, 1H).

Preparation H: methanesulfonic acid2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylester H.i. tert-butyl-dimethyl-[(R)-2-oxiranyl-ethoxy]-silane and(2S)-4-(tert-butyl-dimethyl-silanyloxy)-butane-1,2-diol

The title intermediates were prepared in analogy to Kishi et al., Org.Lett. (2005), 7, 3997, (intermediate S2-3) via hydrolytic kineticresolution of (RS)-tert-butyl-dimethyl-(2-oxiranyl-ethoxy)-silane(prepared according to J. Org. Chem. (2008), 73, 1093). Two compoundswere isolated after CC (Hept/EA 2:1).

First eluting compound:tert-butyl-dimethyl-[(R)-2-oxiranyl-ethoxy]-silane (colourless oil, 25.3g, 48% yield). ¹H NMR (CDCl₃) δ: 3.77 (t, J=6.4 Hz, 2H), 3.04 (m, 1H),2.78 (m, 1H), 2.51 (dd, J=5.0, 2.9 Hz, 1H), 1.74 (m, 2H), 0.90 (d, J=0.6Hz, 9H), 0.06 (s, 6H).

Second eluting compound:(2S)-4-(tert-butyl-dimethyl-silanyloxy)-butane-1,2-diol (colourless oil,24.9 g, 43% yield). ¹H NMR (CDCl₃) δ: 3.89 (m, 3H), 3.62 (s, 1H), 3.53(m, 1H), 3.42 (br. s, 1H), 2.29 (m, 1H), 1.70 (m, 2H), 0.90 (s, 9H),0.09 (s, 6H).

H.ii. Toluene-4-sulfonic acid(S)-4-(tert-butyl-dimethyl-silanyloxy)-2-hydroxy-butyl ester

To a solution of (2S)-4-(tert-butyl-dimethyl-silanyloxy)-butane-1,2-diol(23.9 g, 108 mmol, second eluting compound in H.i and DMAP (2.65 g, 0.2eq.) in DCM (80 mL) cooled to 0° C. were added TEA (43.8 mL, 2.9 eq.)and a solution of pTsCl (20.7 g, 1.1 eq.) in DCM (15 mL). The mixturewas stirred at rt for 5 h, poured into sat. aq. NaHCO₃ and extractedwith DCM. The org. layer was dried over MgSO₄ and concentrated. Theresidue was purified by CC (Hept/EA 2:1) to afford the titleintermediate as a colourless oil (31.3 g, 77% yield).

¹H NMR (CDCl₃) δ: 7.80 (d, J=7.6 Hz, 2H), 7.34 (d, J=7.6 Hz, 2H), 4.02(m, 3H), 3.80 (m, 2H), 2.45 (s, 3H), 1.70 (m, 2H), 1.27 (m, 1H), 0.87(s, 9H), 0.05 (s, 6H).

H.iii. (2S)-tert-butyl-dimethyl-(2-oxiranyl-ethoxy)-silane

2M NaOH (35 mL) was added to a solution of intermediate H.ii (31.1 g,83.1 mmol) in THF (350 mL) and the resulting mixture was vigorouslystirred at rt for 3 h. The mixture was taken in 1M NaOH (200 mL) andextracted with TBME (2×). The combined org. layers were washed withwater and brine, dried over MgSO₄ and concentrated. The resulting oilwas purified by Kugelrohr-distillation (ca. 70° C. at 0.1 mbar) toafford the title intermediate as a colourless oil (14.7 g, 87% yield).

¹H NMR (CDCl₃) δ: 3.77 (t, J=6.4 Hz, 2H), 3.04 (m, 1H), 2.78 (m, 1H),2.51 (dd, J=5.0, 2.9 Hz, 1H), 1.74 (m, 2H), 0.90 (d, J=0.6 Hz, 9H), 0.06(s, 6H).

H.iv.6-[(S)-4-(tert-butyl-dimethyl-silanyloxy)-2-hydroxy-butylamino]-4H-benzo[1,4]oxazin-3-one

A solution of 6-amino-4H-benzo[1,4]oxazin-3-one (5.03 g, 30.6 mmol;commercial) and intermediate H.iii (6.2 g, 1 eq.) in EtOH/H₂O (9:1; 180mL) was heated at 80° C. for 2 days. The mixture was concentrated underreduced pressure. Residual starting aniline could be removed by additionof Et₂O/MeOH followed by filtration. The filtrate containing the productwas concentrated under reduced pressure to afford the title intermediateas a brown oil (9.45 g, 84% yield) which was used as such in the nextstep.

MS (ESI, m/z): 367.2 [M+H⁺].

H.v.6-{(S)-5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]oxazin-3-one

Starting from intermediate H.iv (9.4 g, 25.6 mmol), and using procedureI, the title intermediate was obtained as a beige solid (2.40 g, 24%yield) after CC (DCM/MeOH/NH₄OH 1000:50:4).

MS (ESI, m/z): 393.4 [M+H⁺].

H.vi.6-[(S)-5-(2-hydroxy-ethyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]oxazin-3-one

Starting from intermediate H.v (2.40 g, 6.11 mmol) and using procedureJ, the title intermediate was obtained as an off-white solid (0.82 g,48% yield) after trituration with Et₂O/EA.

MS (ESI, m/z): 279.5 [M+H⁺].

H.vii. Methanesulfonic acid2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylester

Starting from intermediate H.vi (0.82 g, 2.95 mmol) and using procedureH, the title compound was obtained as a beige solid (0.61 g, 58% yield).

¹H NMR (DMSO-d6) δ: 10.72 (s, 1H), 7.30 (d, J=2.1 Hz, 1H), 6.93 (m, 2H),4.76 (m, 1H), 4.52 (s, 2H), 4.34 (m, 2H), 4.11 (t, J=8.8 Hz, 1H), 3.72(m, 1H), 3.20 (s, 3H), 2.17 (m, 2H).

MS (ESI, m/z): 357.3 [M+H⁺].

Preparation I: methanesulfonic acid2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylester I.i.6-[(R)-4-(tert-butyl-dimethyl-silanyloxy)-2-hydroxy-butylamino]-4H-benzo[1,4]oxazin-3-one

A solution of 6-amino-4H-benzo[1,4]oxazin-3-one (commercial; 6.49 g,39.5 mmol) and tert-butyl-dimethyl-[(R)-2-oxiranyl-ethoxy]-silane (firsteluting compound in step H.i; 8.0 g, 39.5 mmol) in EtOH/H₂O (9:1; 240mL) was heated at 80° C. for 2 days. The mixture was concentrated underreduced pressure. Residual starting aniline could be removed by additionof Et₂O/MeOH followed by filtration. The filtrate containing the productwas concentrated under reduced pressure and the residue was purified byCC (DCM/MeOH/NH₄OH 1000:50:4) to afford the title intermediate as abrown oil (5.82 g, 40% yield).

MS (ESI, m/z): 367.3 [M+H⁺].

I.ii.6-{(R)-5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]oxazin-3-one

Starting from intermediate I.i (5.8 g, 15.8 mmol) and using procedure I,the title intermediate was obtained as a beige solid (2.7 g, 43% yield)after trituration with Et₂O/EA/MeOH.

MS (ESI, m/z): 393.5 [M+H⁺].

I.iii.6-[(R)-5-(2-hydroxy-ethyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]oxazin-3-one

Starting from intermediate I.ii (2.70 g, 6.88 mmol) and using procedureJ, the title intermediate was obtained as an off-white solid (1.25 g,65% yield) after trituration with Et₂O/MeOH.

MS (ESI, m/z): 279.5 [M+H⁺].

I.iv. Methanesulfonic acid2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylester

Starting from intermediate I.iii (2.1 g, 7.55 mmol) and using procedureH, the title compound was obtained as an off-white solid (1.16 g, 43%yield).

MS (ESI, m/z): 357.2 [M+H⁺].

Preparation J: methanesulfonic acid2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylester J.i.6-[(R)-4-(tert-butyl-dimethyl-silanyloxy)-2-hydroxy-butylamino]-4H-benzo[1,4]thiazin-3-one

A solution of 6-amino-4H-benzo[1,4]thiazin-3-one (10.68 g, 59.3 mmol;commercial) and tert-butyl-dimethyl-[(R)-2-oxiranyl-ethoxy]-silane(first eluting compound in step H.i.; 12.0 g, 59.3 mmol) in EtOH/H₂O(9:1; 320 mL) was heated at 80° C. for 2 days. The mixture wasconcentrated under reduced pressure. Residual starting aniline could beremoved by addition of Et₂O/MeOH followed by filtration. The filtratecontaining the product was concentrated under reduced pressure to affordthe title intermediate as a brown oil (18.8 g, 83% yield) which was usedas such in the next step.

MS (ESI, m/z): 383.2 [M+H⁺].

J.ii.6-{(R)-5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one

Starting from intermediate J.i (23.5 g, 49.1 mmol) and using procedureI, the title intermediate was obtained as a colourless solid (8.4 g, 42%yield) after CC (DCM/MeOH/NH₄OH 1000:50:4).

MS (ESI, m/z): 409.3 [M+H⁺].

6-[(R)-5-(2-hydroxy-ethyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-one

Starting from intermediate J.ii (8.4 g, 20.6 mmol) and using procedureJ, the title intermediate was obtained as an off-white solid (4.79 g,79% yield) after trituration with Et₂O/EA.

MS (ESI, m/z): 295.5 [M+H⁺].

J.iv. Methanesulfonic acid2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylester

Starting from intermediate J.iii (4.7 g, 16.0 mmol) and using procedureH, the title compound was obtained as an off-white solid (5.80 g, 98%yield) after CC (DCM/MeOH/NH₄OH 1000:50:4).

MS (ESI, m/z): 373.4 [M+H⁺].

Preparation K:6-[(S)-5-(2-iodo-ethyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-oneK.i.6-[(S)-4-(tert-butyl-dimethyl-silanyloxy)-2-hydroxy-butylamino]-4H-benzo[1,4]thiazin-3-one

A solution of 6-amino-4H-benzo[1,4]thiazin-3-one (8.0 g, 44.5 mmol;commercial) and intermediate H.iii (9.0 g, 1 eq.) in 9-1 EtOH/H₂O (250mL) was heated at 80° C. for 2 days. The mixture was concentrated underreduced pressure. Residual starting aniline could be removed by additionof Et₂O/MeOH followed by filtration. The filtrate containing the productwas concentrated under reduced pressure to afford the title intermediateas a brown oil (14.58 g, 86% yield) which was used as such in the nextstep.

MS (ESI, m/z): 383.2 [M+H⁺].

K.ii.6-{(S)-5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one

Starting from intermediate K.i (14.5 g, 37.9 mmol) and using procedureI, the title intermediate was obtained as a colourless solid (5.56 g,36% yield) after CC (DCM/MeOH/NH₄OH 1000:50:4).

MS (ESI, m/z): 409.3 [M+H⁺].

K.iii.6-[(S)-5-(2-hydroxy-ethyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-one

Starting from intermediate K.ii (5.50 g, 13.6 mmol) and using procedureJ, the title intermediate was obtained as an off-white solid (3.08 g,77% yield) after trituration with Et₂O/EA.

MS (ESI, m/z): 295.5 [M+H⁺].

K.iv. Methanesulfonic acid2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylester

Starting from intermediate K.iii (3.0 g, 10.2 mmol) and using procedureH, the title intermediate was obtained as an off-white solid (3.64 g,96% yield) after trituration with ether.

MS (ESI, m/z): 373.4 [M+H⁺].

K.v.6-[(S)-5-(2-iodo-ethyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-one

Starting from intermediate K.iv (2.5 g, 6.7 mmol) and using procedure K,the title compound was obtained as a slightly orange solid (2.11 g, 78%yield) after trituration with Et₂O/EA.

¹H NMR (DMSO-d6) δ: 10.55 (s, 1H), 7.30 (m, 2H), 7.04 (dd, J=8.5, 2.3Hz, 1H), 4.68 (m, 1H), 4.10 (t, J=8.8 Hz, 1H), 3.70 (dd, J=8.8, 6.7 Hz,1H), 3.41 (s, 2H), 3.29 (m, 2H), 2.23 (m, 2H).

MS (ESI, m/z): 405.1 [M+H⁺].

Preparation L:6-[(R)-5-(2-iodo-ethyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-one

Starting from intermediate J.iv (3.5 g, 9.4 mmol) and using procedure K,the title compound was obtained as an off-white solid (3.52 g, 93%yield) after trituration with Et₂O/EA.

¹H NMR (DMSO-d6) δ: 10.55 (s, 1H), 7.30 (m, 2H), 7.04 (dd, J=8.5, 2.3Hz, 1H), 4.68 (m, 1H), 4.10 (t, J=8.8 Hz, 1H), 3.70 (dd, J=8.8, 6.7 Hz,1H), 3.41 (s, 2H), 3.29 (m, 2H), 2.23 (m, 2H).

MS (ESI, m/z): 405.0 [M+H⁺].

Preparation M: (RS)-methanesulfonic acid2-[2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylester M.i.(RS)-6-[4-(tert-butyl-dimethyl-silanyloxy)-2-hydroxy-butylamino]-4H-benzo[1,4]thiazin-3-one

A solution of 6-amino-4H-benzo[1,4]thiazin-3-one (3.56 g, 19.8 mmol;commercial) and (RS)-tert-butyl-dimethyl-(2-oxiranyl-ethoxy)-silane(prepared according to J. Org. Chem. (2008), 73, 1093; 4.0 g, 19.8 mmol)in EtOH/H₂O (9:1; 140 mL) was heated at 80° C. for 2 days. The mixturewas concentrated under reduced pressure and the residue was purified byCC (DCM/MeOH/NH₄OH 1000:50:4) to afford the title intermediate as abrown oil (2.20 g, 29% yield).

MS (ESI, m/z): 383.2 [M+H⁺].

M.ii.(RS)-6-{5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one

Starting from intermediate M.i (2.20 g, 5.75 mmol) and using procedureI, the title intermediate was obtained as a pale orange solid (1.53 g,65% yield) after CC (DCM/MeOH/NH₄OH 1000:50:4).

MS (ESI, m/z): 409.4 [M+H⁺].

M.iii.(RS)-6-[5-(2-hydroxy-ethyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-one

Starting from intermediate M.ii (1.50 g, 3.67 mmol) and using procedureJ, the title intermediate was obtained as an off-white solid (0.73 g,68% yield) after trituration with Et₂O/EA.

MS (ESI, m/z): 295.1 [M+H⁺].

M.iv. (RS)-methanesulfonic acid2-[2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylester

Starting from intermediate M.iii (0.70 g, 2.38 mmol) and using procedureH, the title compound was obtained as a beige solid (0.80 g, 90% yield)after CC (DCM/MeOH/NH₄OH 1000:50:4).

MS (ESI, m/z): 373.1 [M+H⁺].

Preparation N:6-((S)-5-iodomethyl-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]thiazin-3-oneN.i. 6-((S)-3-chloro-2-hydroxy-propylamino)-4H-benzo[1,4]thiazin-3-one

A suspension of 6-amino-4H-benzo[1,4]thiazin-3-one (18.0 g, 100 mmol;commercial) and Ca(OTf)₂ (0.5 eq.) in MeCN (800 mL) was heated at 50°for 1 h. (S)-epichlorohydrin (18.5 g, 200 mmol) was added and themixture was stirred at rt for 72 h and at 45° C. for 24 h. The volatileswere removed under reduced pressure. After aqueous workup and extractionwith EA, the title intermediate crystallised from EA to afford a beigesolid (17.38 g, 64% yield).

MS (ESI, m/z): 273.2 [M+H⁺].

N.ii.6-((S)-5-chloromethyl-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]thiazin-3-one

Starting from intermediate N.i (39.3 g, 144 mmol.) and using procedureI, the title intermediate was obtained as a beige solid (34.2 g, 79%yield) after CC (EA/Hept 2:1, EA).

MS (ESI, m/z): 299.1 [M+H⁺].

N.iii.6-((S)-5-iodomethyl-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]thiazin-3-one

Starting from intermediate N.ii (14.0 g, 46.9 mmol) and using procedureK, the title compound was obtained as a pale beige solid (15.0 g, 82%yield).

¹H NMR (DMSO-d6) δ: 10.56 (s, 1H), 7.31 (m, 2H), 7.12 (dd, J=8.5, 2.3Hz, 1H), 4.71 (m, 1H), 4.14 (t, J=9.1 Hz, 1H), 3.59 (m, 3H), 3.31 (s,2H).

MS (ESI, m/z): 391.4 [M+H⁺].

Preparation O:6-((R)-5-iodomethyl-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]thiazin-3-oneO.i. 6-((R)-3-chloro-2-hydroxy-propylamino)-4H-benzo[1,4]thiazin-3-one

A solution of 6-amino-4H-benzo[1,4]thiazin-3-one (18.39 g, 102 mmol;commercial) and (R)-epichlorohydrin (8.0 mL, 1 eq.) in EtOH/H₂O (9:1;450 mL) was heated at 80° C. overnight. The mixture was concentratedunder reduced pressure. Residual starting aniline could be removed byaddition of Et₂O/EA followed by filtration. The filtrate containing theproduct was concentrated under reduced pressure to afford the titleintermediate as a beige solid (22.52 g, 81% yield) which was used assuch in the next step.

MS (ESI, m/z): 273.2 [M+H⁺].

O.ii.6-((R)-5-chloromethyl-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]thiazin-3-one

Starting from intermediate O.i (22.0 g, 81.0 mmol) and using procedureI, the title intermediate was obtained as a yellow solid (8.79 g, 36%yield) after trituration with DCM/MeOH.

MS (ESI, m/z): 299.1 [M+H⁺].

O.iii.6-((R)-5-iodomethyl-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]thiazin-3-one

Starting from intermediate O.ii (8.75 g, 29 mmol) and using procedure K,the title compound was obtained as an off-white solid (9.27 g, 81%yield) after trituration with Et₂O/EA.

¹H NMR (DMSO-d6) δ: 10.56 (s, 1H), 7.31 (m, 2H), 7.12 (dd, J=8.5, 2.3Hz, 1H), 4.71 (m, 1H), 4.14 (t, J=9.1 Hz, 1H), 3.59 (m, 3H), 3.31 (s,2H).

MS (ESI, m/z): 390.9 [M+H⁺].

Preparation P:(S)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-5-iodomethyl-oxazolidin-2-oneP.i.(S)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-5-hydroxymethyl-oxazolidin-2-one

A solution of (2,3-dihydro-benzo[1,4]dioxin-6-yl)-carbamic acid benzylester (13.0 g, 45.6 mmol) in THF (220 mL) was cooled to −78° C. beforethe dropwise addition of n-BuLi (29.5 mL of a 2.3M solution in Hex, 1.1eq.). The mixture was stirred at −78° C. for 1 h and then warmed to −15°C. and treated dropwise with (S)-glycidyl butyrate (7.37 g, 1.1 eq.).The mixture was stirred at rt overnight. Cs₂CO₃ (tip of a spatula) wasadded and the mixture heated at 40° C. until complete conversion. Themixture was diluted with EA and washed with a sat. aq. NH₄Cl and water.The org. layer was dried over MgSO₄ and concentrated. The residue waspurified by CC (Hex/EA 2:1, 1:1) to afford the title intermediate as agrey solid (7.04 g, 62% yield).

¹H NMR (DMSO-d6) δ: 7.13 (d, J=2.5 Hz, 1H), 6.96 (dd, J=2.5, 8.9 Hz,1H), 6.86 (d, J=8.9 Hz, 1H), 5.16 (t, J=5.8 Hz, 1H), 4.70-4.50 (m, 1H),4.30-4.10 (m, 4H), 4.10-3.90 (m, 1H), 4.80-4.70 (m, 1H), 4.70-4.60 (m,1H), 4.60-4.50 (m, 1H).

P.ii. Methanesulfonic acid(S)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethylester

Starting from intermediate P.i (7.0 g, 27.9 mmol) and using procedure H,the title intermediate was obtained as a colourless solid (9.0 g, 98%yield).

MS (ESI, m/z): 330.3 [M+H⁺].

P.iii.(S)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-5-iodomethyl-oxazolidin-2-one

Starting from intermediate P.ii (9.0 g, 27.3 mmol) and using procedureK, the title compound was obtained as an off-white solid (6.91 g, 70%yield) after trituration with Et₂O/EA.

¹H NMR (CDCl₃) δ: 7.07 (d, J=2.6 Hz, 1H), 6.98 (dd, J=9.1, 2.6 Hz, 1H),6.85 (d, J=8.9 Hz, 1H), 4.68 (m, 1H), 4.24 (s, 4H), 4.10 (t, J=9.1 Hz,1H), 3.72 (dd, J=9.1, 5.9 Hz, 1H), 3.46 (m, 1H), 3.33 (m, 1H).

MS (ESI, m/z): 362.2 [M+H⁺].

Preparation Q: methanesulfonic acid(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethylester Q.i.6-[(S)-3-(tert-butyl-dimethyl-silanyloxy)-2-hydroxy-propylamino]-4H-benzo[1,4]oxazin-3-one

LiClO₄ (7.20 g, 3 eq.) was added to a solution oftert-butyl-dimethyl-((S)-1-oxiranylmethoxy)-silane (commercial; 4.25 g,22.6 mmol) in MeCN (70 mL). 6-amino-4H-benzo[1,4]oxazin-3-one(commercial; 3.70 g, 1 eq.) was then added and the mixture was stirredat 50° C. for 6 h. The solvent was removed under reduced pressure andthe residue was purified by CC (DCM/MeOH/NH₄OH 1000/25/2) to afford thetitle intermediate as a pale brown foam (5.25 g, 66% yield).

MS (ESI, m/z): 353.3 [M+H⁺].

Q.ii.6-[(S)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]oxazin-3-one

Starting from intermediate Q.i (10.24 g, 29 mmol) and using procedure I,the title intermediate was obtained as a pale yellow solid (6.30 g, 57%yield) after trituration with ether.

MS (ESI, m/z): 379.2 [M+H⁺].

Q.iii.6-((S)-5-hydroxymethyl-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]oxazin-3-one

Starting from intermediate Q.ii (6.30 g, 16.6 mmol) and using procedureJ, the title intermediate was obtained as a colourless solid (3.49 g,79% yield) after trituration with EA.

MS (ESI, m/z): 265.5 [M+H⁺].

Q.iv. Methanesulfonic acid(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethylester

A suspension of intermediate Q.iii (4.93 g, 18.7 mmol) in anhydrous DCM(110 mL) was treated with DIPEA (12.0 mL, 3.75 eq.) and the mixture wascooled to 0° C. Ms₂O (4.88 g, 1.5 eq.) was added portionwise. Theresulting mixture was stirred at 0° C. for 15 min. Water was added andstirring was continued for 15 min at rt. The precipitated product wasfiltered, washed with water and DCM. The thus obtained solid wastriturated with DCM/MeOH/NH₄OH (1000:25:2) to give the titleintermediate as a colourless solid (3.785 g, 60% yield).

¹H NMR (DMSO-d6) δ: 10.72 (s, 1H), 7.29 (dd, J=2.1, 0.6 Hz, 1H), 6.94(m, 2H), 4.95 (m, 1H), 4.52 (s, 2H), 4.49 (m, 2H), 4.11 (t, J=9.1 Hz,1H), 3.73 (m, 2H), 3.23 (s, 3H).

MS (ESI, m/z): 343.3 [M+H⁺].

Preparation R:(S)-3-(3-fluoro-4-methyl-phenyl)-5-iodomethyl-oxazolidin-2-one R.i.(S)-3-(3-fluoro-4-methyl-phenyl)-5-hydroxymethyl-oxazolidin-2-one

A mixture of 3-fluoro-4-methyl-aniline (commercial; 1.25 g, 10 mmol),sat. aq. NaHCO₃ (10 mL) and acetone (10 mL) was treated dropwise withbenzyl chloroformate (1.70 g, 1.41 mL, 1 eq.). After CO₂ evolutionceased, the mixture was partitioned between EA and sat. aq. NaHCO₃, theorg. layer was dried over MgSO₄ and concentrated under reduced pressure.The resulting benzyl carbamate was dissolved in THF (50 mL) and cooledunder argon to −78° C. n-BuLi (2.5M in Hex, 6.45 mL, 1.1 eq.) was addeddropwise, and the resulting solution was stirred for 1 h at thattemperature. The reaction was then allowed to warm to −15° C. at which(S)-glycidyl butyrate (1.69 mL, 1.1 eq.) was added dropwise. The mixturewas stirred at rt overnight. A tip of a spatula of Cs₂CO₃ was added, andthe mixture was stirred at rt for 3 h. NH₄Cl and EA were added and thephases were separated. The aq. phase was extracted once more with EA andthe combined org. extracts were washed several times with sat. aq.NH₄Cl, then with brine, dried over Na₂SO₄ and concentrated. The orangesolid obtained was triturated with EA to afford the title intermediateas a pale yellow solid (1.18 g, 53% yield).

MS (ESI, m/z): 226.3 [M+H⁺].

R.ii. Methanesulfonic acid(S)-3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl ester

Starting from intermediate R.i (4.70 g, 20.9 mmol) and followingprocedure H the title intermediate was obtained as a yellow solid (6.37g, 100% yield) after trituration in ether.

¹H NMR (CDCl₃) δ: 7.36 (dd, J=11.7, 2.3 Hz, 1H), 7.13 (m, 2H), 4.91 (m,1H), 4.46 (m, 2H), 4.13 (t, J=9.1 Hz, 1H), 3.92 (dd, J=9.1, 6.2 Hz, 1H),3.10 (s, 3H), 2.25 (d, J=1.8 Hz, 3H).

MS (ESI, m/z): 330.3 [M+H⁺].

R.iii. (S)-3-(3-fluoro-4-methyl-phenyl)-5-iodomethyl-oxazolidin-2-one

Starting from intermediate R.ii (6.30 g, 20.8 mmol) and using procedureK, the title compound was obtained as a slightly pink solid (6.3 g, 91%yield) after trituration with Et₂O/EA.

¹H NMR (CDCl₃) δ: 7.36 (dd, J=12.0, 2.1 Hz, 1H), 7.16 (m, 2H), 4.73 (m,1H), 4.14 (m, 1H), 3.76 (dd, J=9.4, 6.2 Hz, 1H), 3.48 (m, 1H), 3.35 (dd,J=10.3, 8.2 Hz, 1H), 2.25 (d, J=1.8 Hz, 3H).

MS (ESI, m/z): 335.8 [M+H⁺].

Preparation S: (RS)-methanesulfonic acid2-[3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-yl]-ethyl ester S.i.(RS)-4-(tert-butyl-dimethyl-silanyloxy)-1-(3-fluoro-4-methyl-phenylamino)-butan-2-ol

To a solution of (RS)-tert-butyl-dimethyl-(2-oxiranyl-ethoxy)-silane(4.4 g, 200 mmol; prepared as in J. Org. Chem. (2008), 73, 1093) in MeCN(60 mL) was added LiClO₄ (6.31 g, 3 eq.). 3-fluoro-4-methylaniline(commercial; 2.28 g, 0.92 eq.) was added and the mixture was stirred at50° C. for 5 h. The solvent was removed under reduced pressure and theresidue was purified by CC (DCM/MeOH/NH₄OH 1000:25:2) to afford thetitle intermediate as a brown oil (5.56 g, 86% yield).

MS (ESI, m/z): 328.4 [M+H⁺].

S.ii.(RS)-5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-3-(3-fluoro-4-methyl-phenyl)-oxazolidin-2-one

Starting from intermediate S.i (2.50 g, 7.63 mmol) and using procedureI, the title intermediate was obtained as an off-white solid (1.22 g,45% yield) after trituration with ether/EA.

MS (ESI, m/z): 354.2 [M+H⁺].

S.iii.(RS)-3-(3-fluoro-4-methyl-phenyl)-5-(2-hydroxy-ethyl)-oxazolidin-2-one

Starting from intermediate S.ii (1.20 g, 3.40 mmol) and using procedureJ, the title intermediate was obtained as a colourless solid (0.478 g,59% yield) after trituration with Et₂O/EA/DCM.

MS (ESI, m/z): 240.1 [M+H⁺].

S.iv. (RS)-methanesulfonic acid2-[3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-yl]-ethyl ester

Starting from intermediate S.iii (470 mg, 2.0 mmol) and using procedureH, the title compound was obtained as an off-white solid (0.60 g, 96%yield) after CC (DCM/MeOH/NH₄OH 1000:50:4).

MS (ESI, m/z): 318.2 [M+H⁺].

Preparation T:3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propionaldehydeT.i.6-[(R)-5-(tert-butyl-dimethyl-silanyloxy)-2-hydroxy-pentylamino]-4H-benzo[1,4]oxazin-3-one

A mixture of (R)-tert-butyl-dimethyl-(3-oxiranyl-propoxy)-silane (13 g,60 mmol; prepared according to Org. Lett. (2005), 7, 3997) and6-amino-4H-benzo[1,4]oxazin-3-one (9.9 g) in EtOH/H₂O (9:1, 325 mL) washeated at reflux overnight. The volatiles were removed under reducedpressure and the residue purified by CC (Hept/EA 1:1) to give thedesired intermediate as a brown oil (8.9 g, 39% yield).

MS (ESI, m/z): 318.2 [M+H⁺].

T.ii.6-{(R)-5-[3-(tert-butyl-dimethyl-silanyloxy)-propyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]oxazin-3-one

Starting from intermediate T.i (8.8 g, 23 mmol) and using procedure I,the title intermediate was obtained as an orange solid (9.8 g, quant.)after crystallisation from Hept/EA.

MS (ESI, m/z): 407.6 [M+H⁺].

T.iii.6-[(R)-5-(3-hydroxy-propyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-one

Starting from intermediate T.ii (9.8 g, 24 mmol) and using procedure J,the title intermediate was obtained as a yellowish solid (5.0 g, 71%yield) after CC (EA, EA/MeOH 9:1) followed by crystallisation fromether/EA.

MS (ESI, m/z): 293.3 [M+H⁺].

T.iv.3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propionaldehyde

To a solution of intermediate T.iii (292 mg, 1 mmol) and DIPEA (0.5 mL,3 eq.) in DCM (5 mL) at rt was added dropwise a solution of SO₃.pyridinecomplex (318 mg, 2 eq.) in DMSO (1 mL) over 10 min. The mixture wasstirred at rt for 2 h, diluted with DCM and washed with water. The org.phase was washed several times with water, dried over MgSO₄ andconcentrated to give the desired aldehyde as a beige solid (260 mg, 90%yield).

¹H NMR (DMSO-d6) δ: 10.71 (s, 1H) 9.68 (d, J=0.9 Hz, 1H), 7.31 (s, 1H),6.92 (m, 2H), 4.64 (m, 1H), 4.52 (d, J=1.2 Hz, 2H), 4.07 (m, 1H), 3.66(m, 1H), 2.60 (m, 2H), 1.98 (m, 2H).

Preparation U:3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propionaldehydeU.i.6-[(R)-5-(tert-butyl-dimethyl-silanyloxy)-2-hydroxy-pentylamino]-4H-benzo[1,4]thiazin-3-one

A mixture of (R)-tert-butyl-dimethyl-(3-oxiranyl-propoxy)-silane (13 g,60 mmol; prepared as in Org. Lett. (2005), 7, 3997) and6-amino-4H-benzo[1,4]thiazin-3-one (10.8 g) in EtOH/H₂O (9:1, 325 mL)was heated at reflux overnight. The volatiles were removed under reducedpressure and the residue purified by CC (Hept/EA 1:1) to give thedesired intermediate as a brown oil (6.8 g, 28% yield).

MS (ESI, m/z): 397.1 [M+H⁺].

U.ii.6-{(R)-5-[3-(tert-butyl-dimethyl-silanyloxy)-propyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one

Starting from intermediate U.i (6.7 g, 17 mmol) and using procedure I,the title intermediate was obtained as an orange solid (7.8 g, quant.)after crystallisation from Hept/EA.

MS (ESI, m/z): 423.4 [M+H⁺].

U.iii.6-[(R)-5-(3-hydroxy-propyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-one

Starting from intermediate U.ii (7.1 g, 16.8 mmol) and using procedureJ, the title intermediate was obtained as a yellowish solid (3.1 g, 60%yield) after CC (EA. EA/MeOH 9:1).

MS (ESI, m/z): 309.1 [M+H⁺].

U.iv.3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propionaldehyde

To a solution of intermediate U.iii (500 mg, 1.6 mmol) and DIPEA (0.83mL, 3 eq.) in DCM (7 mL) at rt was added dropwise a solution ofSO₃.pyridine complex (516 mg, 2 eq.) in DMSO (1.7 mL) over 10 min. Themixture was stirred at rt for 2 h, diluted with DCM and washed withwater. The org. phase was washed several times with water, dried overMgSO₄ and concentrated to give the desired aldehyde after triturationwith ether/EA as a beige solid (440 mg, 88% yield).

MS (ESI, m/z): 307.5 [M+H⁺].

Preparation V:(R)-4-aminomethyl-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-oneV.i. 2-(6-methoxy-[1,5]naphthyridin-4-yl)-propane-1,3-diol

A mixture of 2-methoxy-8-methyl-[1,5]naphthyridine (2.90 g, 16.6 mmol;prepared according to WO 00/21948) and formaldehyde (37% in water, 7.8mL) was heated at 100° C. for 3 days and at 110° C. for 2 days. Aftercooling to rt, the mixture was concentrated, taken up in MeOH andconcentrated again. The residue was purified by CC (DCM/MeOH/NH₄OH1000:100:8) to afford the title intermediate as a pale beige solid (2.78g, 71% yield).

¹H NMR (DMSO-d₆) δ: 8.67 (d, J=4.4 Hz, 1H), 8.22 (d, J=9.1 Hz, 1H), 7.51(d, J=4.4 Hz, 1H), 7.22 (d, J=9.1 Hz, 1H), 4.56 (m, 2H), 4.00 (s, 3H),3.84 (m, 3H).

V.ii. Acetic acid(S)-3-hydroxy-2-(6-methoxy-[1,5]naphthyridin-4-yl)-propyl ester

A 0.5M solution of intermediate V.i (5.45 g, 23.3 mmol) in vinyl acetate(60 mL) was treated with powdered 3 Å molecular sieves (350 mg) andstirred at rt for 15 min under a nitrogen atmosphere. Lipase fromCandida antarctica (2.69 g, bound to acrylic resin) was added andstirring was continued for 4 h at rt. The mixture was filtered; thefilter cake was washed with EA and the filtrate was concentrated. Theresidue was purified by CC (DCM/MeOH/NH₄OH 1000:25:2) to afford thetitle intermediate as a colourless oil (2.70 g, 42% yield). Thecorresponding diacetate (3.81 g, 51% yield) was then afterwards cleavedback to the diol and used again as substrate.

¹H NMR (CDCl₃) δ: 8.72 (d, J=4.4 Hz, 1H), 8.23 (d, J=9.1 Hz, 1H), 7.46(d, J=4.4 Hz, 1H), 7.14 (d, J=9.1 Hz, 1H), 4.65 (m, 2H), 4.22 (m, 1H),4.07 (m, 4H), 2.96 (m, 1H), 2.04 (s, 1H).

MS (ESI, m/z): 277.3 [M+H⁺].

Alternative α:

V.iii. Acetic acid(S)-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de][1,5]naphthyridin-4-ylmethylester

TEA (2.1 mL, 2 eq.) and MsCl (0.70 mL, 1.2 eq.) were added at 0° C. to asolution of intermediate V.ii (2.05 g, 7.41 mmol) in DCM (40 mL). Thereaction was stirred for 20 min at this temperature. DCE (40 mL) wasadded and the solution was slowly warmed to 60° C. and let stir at thistemperature for 4 h. After cooling to rt, water was added and the twolayers were decanted and the aq. layer was extracted once more with DCM.The combined org. layers were concentrated to dryness. The residue wastriturated with TBME to afford the title intermediate as a grey solid(1.40 g, 77% yield).

¹H NMR (CDCl₃) δ: 8.52 (d, J=4.7 Hz, 1H), 7.93 (d, J=9.7 Hz, 1H), 7.34(d, J=4.7 Hz, 1H), 6.89 (d, J=9.7 Hz, 1H), 4.56 (dd, J=12.9, 9.4 Hz,1H), 4.36 (m, 2H), 4.27 (dd, J=13.2, 5.0 Hz, 1H), 4.10 (m, 1H), 2.06 (s,3H).

MS (ESI, m/z): 245.2 [M+H⁺].

V.iv.(S)-4-hydroxymethyl-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

K₂CO₃ (0.40 g, 0.5 eq.) was added to a solution of intermediate V.iii(1.40 g, 5.73 mmol) cooled to 0° C. and the resulting mixture wasvigorously stirred at 0° C. for 30 min. The mixture was concentrated andthe residue was purified by CC (DCM/MeOH/NH₄OH 1000:100:8). The productwas triturated with EA/TBME to afford the title intermediate as a greysolid (0.98 g, 85% yield).

MS (ESI, m/z): 203.0 [M+H⁺].

V.v. Methanesulfonic acid(S)-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de][1,5]naphthyridin-4-ylmethylester

A solution of intermediate V.iv (0.33 g, 1.63 mmol) and TEA (0.57 mL,2.5 eq.) in anhydrous DCM (15 mL) was cooled to 0° C. and treateddropwise with MsCl (0.19 mL, 1.5 eq.). The resulting mixture was stirredat 0° C. for 1 h. Water and DCM were added and the phases separated. Theorg. layer was dried over MgSO₄ and concentrated under reduced pressureto afford the title intermediate as a colourless gum (0.40 g, 88% yield)which was used in the next step without further purification.

MS (ESI, m/z): 281.3 [M+H⁺].

V.vi.(R)-4-aminomethyl-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

A solution of intermediate V.v (0.35 g, 1.24 mmol) in DMF (12 mL) wastreated with sodium azide (0.65 g, 8 eq.) and stirred at 50° C. for 1.5h. After cooling to rt, water was added and the mixture was extractedwith DCM. The org. layer was dried over MgSO₄ and concentrated underreduced pressure to give a yellow oil (crude azide) which was taken upin THF (1.5 mL). PPh₃ (390 mg) and water (0.13 mL) were added and themixture was heated at 50° C. for 3 h. The reaction mixture wasconcentrated to dryness and the residue was purified by CC(DCM/MeOH/NH₄OH 1000:100:8) to afford the title intermediate as a yellowoil (30 mg, 12% yield).

MS (ESI, m/z): 202.2 [M+H⁺].

Alternative β:

V.ii. Acetic acid(R)-3-(tert-butyl-dimethyl-silanyloxy)-2-(6-methoxy-[1,5]naphthyridin-4-yl)-propylester

To a solution of intermediate V.ii (1.66 g) in DCM (50 mL) were addedimidazole (1 eq.) and TBDMSCl (1 eq.). The mixture was stirred at rt for3 h. Another eq. of each reagent was added and the reaction was completeafter 15 min. Water was added and the mixture was extracted with DCM.The org. layer was dried over MgSO₄ and concentrated to afford the titleintermediate as a colourless oil (2.36 g, 100% yield).

MS (ESI, m/z): 391.5 [M+H⁺].

V.iii.(R)-3-(tert-butyl-dimethyl-silanyloxy)-2-(6-methoxy-[1,5]naphthyridin-4-yl)-propan-1-ol

A suspension of intermediate V.vii (2.36 g) and K₂CO₃ (3.34 g) in MeOH(50 mL) was vigorously stirred at rt for 30 min. Water and DCM wereadded. The two layers were decanted and the aq. layer was extracted oncemore with DCM. The combined org. layers were dried over MgSO₄, filteredand concentrated to dryness to afford the title intermediate as acolourless oil (2.1 g, 100% yield).

MS (ESI, m/z): 349.1 [M+H⁺].

V.ix.8-[(R)-2-azido-1-(tert-butyl-dimethyl-silanyloxymethyl)-ethyl]-2-methoxy-[1,5]naphthyridine

Starting from intermediate V.viii (2.09 g) and following procedure N,the title intermediate was isolated as a colourless oil (1.79 g, 80%yield).

MS (ESI, m/z): 374.1 [M+H⁺].

V.x.[(R)-3-(tert-butyl-dimethyl-silanyloxy)-2-(6-methoxy-[1,5]naphthyridin-4-yl)-propyl]-carbamicacid tert-butyl ester

Starting from intermediate V.ix (1.79 g) and using procedure F andprocedure G, the title intermediate was obtained as a dark oil (2.14 g,100% yield).

MS (ESI, m/z): 448.2 [M+H⁺].

V.xi.[(R)-3-hydroxy-2-(6-methoxy-[1,5]naphthyridin-4-yl)-propyl]-carbamicacid tert-butyl ester

Starting from intermediate V.x (2.14 g) and using procedure J, the titleintermediate was obtained as a colourless solid (1.14 g, 72% yield).

MS (ESI, m/z): 334.2 [M+H⁺].

V.xii.((R)-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de][1,5]naphthyridin-4-ylmethyl)-carbamicacid tert-butyl ester

Starting from intermediate V.xi (1.14 g) and using procedure H followedby heating at 60° C. for 2 h in DCE, the title intermediate was obtainedas a colourless solid (0.91 g, 88% yield).

MS (ESI, m/z): 302.2 [M+H⁺].

V.xiii.(R)-4-aminomethyl-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from intermediate V.xi (0.91 g) and using procedure B, thetitle intermediate was obtained as a pale yellow solid (0.496 g, 82%yield).

MS (ESI, m/z): 202.1 [M+H⁺].

Preparation W: (RS)-methanesulfonic acid7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de][1,5]naphthyridin-4-ylmethyl esterW.i.3-(tert-butyl-dimethyl-silanyloxy)-2-(6-methoxy-[1,5]naphthyridin-4-yl)-propan-1-ol

A solution of the intermediate V.i (1.10 g) in THF (55 mL) was treatedat 0° C. with imidazole (351 mg) and a solution of TBDMSCl (707 mg) inTHF (10 mL). After stirring at rt for 2 days, the reaction mixture wasdiluted with EA and extracted with water and brine. The org phase wasdried over MgSO₄ and purified by CC (Hept/EA 1.1 to 0:1), affording acolourless oil (570 mg; 35% yield).

MS (ESI, m/z): 349.2 [M+H⁺].

W.ii. Methanesulfonic acid3-(tert-butyl-dimethyl-silanyloxy)-2-(6-methoxy-[1,5]naphthyridin-4-yl)-propylester

Starting from intermediate W.i (1.4 g) and MsCl (0.374 mL) and usingprocedure H, the title compound was obtained as a yellow oil (1.4 g, 81%yield).

¹H NMR (CDCl₃) δ: 8.72 (d, J=4.4 Hz, 1H) 8.23 (d, J=9.1 Hz, 1H), 7.50(d, J=4.7 Hz, 1H), 7.15 (d, J=9.1 Hz, 1H), 4.78 (m, 2H), 4.44 (m, 1H),4.05 (m, 5H), 2.90 (s, 3H), 0.87 (m, 12H), −0.02 (d, J=8.5 Hz, 6H).

W.iii.4-(tert-butyl-dimethyl-silanyloxymethyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

A solution of intermediate W.ii (1.4 g) in DCE (20 mL) was heated at 85°C. overnight. The reaction mixture was evaporated under reducedpressure. The residue was purified by CC (EA to EA/MeOH 9:1), affordinga colourless oil (340 mg; 33% yield).

MS (ESI, m/z): 317.1 [M+H⁺].

W.iv.4-hydroxymethyl-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from intermediate W.iii (330 mg) and using procedure J, thetitle compound was obtained as a colourless solid (90 mg, 43% yield).

MS (ESI, m/z): 203.2 [M+H⁺].

W.v. (RS)-methanesulfonic acid7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de][1,5]naphthyridin-4-ylmethyl ester

Starting from intermediate W.iv (90 mg) and using procedure H, the titlecompound was obtained as a yellow solid (90 mg, 72% yield).

Analytical data identical to the (S)-enantiomer (intermediate V.v).

Preparation X: rac-1-amino-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-oneX.i. 2-azido-2-(2-methoxy-quinolin-8-yl)-ethanol

A solution of 2-methoxy-8-(2-oxiranyl)-quinoline (900 mg; preparedaccording to WO 2006/046552) in dioxane/water (5:1; 60 mL) was reactedwith NaN₃ at 90° C. for 5 h. The solvents were removed under reducedpressure and the residue was purified by CC (Hex/EA 2:1 to 1:1),affording a yellow oil (480 mg; 44% yield).

MS (ESI, m/z): 245.0 [M+H⁺].

X.ii. rac-2-amino-2-(2-methoxy-quinolin-8-yl)-ethanol

Starting from intermediate X.i (470 mg) and using procedure F, the titlecompound was obtained as a yellow oil (450 mg; 100% yield).

MS (ESI, m/z): 219.1 [M+H⁺].

X.iii. rac-[2-hydroxy-1-(2-methoxy-quinolin-8-yl)-ethyl]-carbamic acidtert-butyl ester

Starting from intermediate X.ii (430 mg) and using procedure G, thetitle compound was obtained as a yellow oil (720 mg; quant.)

MS (ESI, m/z): 319.1 [M+H⁺].

X.iv. rac-methanesulfonic acid2-tert-butoxycarbonylamino-2-(2-methoxy-quinolin-8-yl)-ethyl ester

Starting from intermediate X.iii (700 mg) and using procedure H, thetitle compound was obtained as a yellow oil (900 mg, quant.).

MS (ESI, m/z): 397.0 [M+H⁺].

X.v. rac-(4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamicacid tert-butyl ester

A solution of intermediate X.iv (850 mg) in DCE (10 mL) was heated at85° C. overnight. The solvent was evaporated under reduced pressure,affording a brown oil (780 mg; quant.) which was used without furtherpurification in the next step.

MS (ESI, m/z): 287.1 [M+H⁺].

X.vi. rac-1-amino-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from intermediate X.v (572 mg) and using procedure B, the titlecompound was obtained as a beige solid (230 mg; 62% yield).

MS (ESI, m/z): 187.0 [M+H⁺].

Preparation Y:(S)-4-amino-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one Y.i.(S)-2-azido-2-(6-methoxy-[1,5]naphthyridin-4-yl)-ethanol

This compound was prepared in analogy to Preparation X, step X.i, butstarting from 2-methoxy-8-[(2R)-2-oxiranyl]-1,5-naphthyridine (preparedaccording to WO 02/08224).

The compound was purified by CC (Hept/EA 1:1 to 2:1 to 0:1), affording ayellow solid (3.9 g (87%; contaminated by its region isomer).

MS (ESI, m/z): 246.3 [M+H⁺].

Y.ii. (S)-2-amino-2-(6-methoxy-[1,5]naphthyridin-4-yl)-ethanol

Starting from intermediate Y.i (3.90 g) and using procedure F, the titlecompound was obtained as a yellow oil (2.80 g, 80% yield).

MS (ESI, m/z): 220.0 [M+H⁺].

Y. iii.(S)-[2-hydroxy-1-(6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]-carbamic acidtert-butyl ester

Starting from intermediate Y.ii (2.90 g) and using procedure G, thetitle compound was obtained as a colourless foam (1.40 g, 33% yield).

MS (ESI, m/z): 320.1 [M+H⁺].

Y.iv.((S)-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de][1,5]naphthyridin-4-yl)-carbamicacid tert-butyl ester

Starting from the intermediate Y.iii (1.40 g) and using procedure Hfollowed by heating at 80° C. for 7 h, the title compound was obtainedas a beige solid (570 mg, 45% yield).

MS (ESI, m/z): 288.4 [M+H⁺].

Y.v. (S)-4-amino-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from intermediate Y.iv (570 mg) and using procedure B, thetitle compound was obtained as a beige solid (470 mg, quant.).

¹H NMR (CDCl₃) δ: 8.43 (d, J=4.7 Hz, 1H), 7.79 (d, J=9.7 Hz, 1H), 7.43(dd, J=4.7, 0.9 Hz, 1H), 6.74 (d, J=10.0 Hz, 1H), 4.91 (m, 1H), 4.52(dd, J=13.2, 8.5 Hz, 1H), 4.02 (dd, J=13.5, 4.7 Hz, 1H).

Preparation Z: (S)-6-amino-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-oneZ.i. 2-methoxy-8-vinyl-quinoxaline

A suspension of methyltriphenylphosphonium bromide (22.78 g) in THF (200mL) was treated with tBuOK (7.15 g) and further stirred at rt for 1 h.The mixture was cooled to 0° C. and treated with a solution of3-methoxy-5-quinoxalinecarboxaldehyde (10.0 g; prepared according to WO2006/021448) in THF (100 mL). The mixture was further stirred at rt for3 h, diluted with ether and washed with water and an aq. sat. NH₄Clsolution. The org. phase was dried over MgSO₄ and concentrated underreduced pressure. The residue was crystallized from ether and thecrystals were filtered off. The mother liquor was purified by CC (Hex/EA1:1), affording a light orange solid (8.70 g; 88% yield).

¹H NMR (CDCl₃) δ: 8.48 (s, 1H), 7.92 (m, 2H), 7.78 (dd, J=17.9, 11.1 Hz,1H), 7.54 (m, 1H), 6.03 (dd, J=17.9, 1.5 Hz, 1H), 5.48 (dd, J=11.4, 1.5Hz, 1H), 4.12 (s, 3H).

Z.ii. (R)-1-(3-methoxy-quinoxalin-5-yl)-ethane-1,2-diol

Starting from intermediate Z.i (8.70 g) and using procedure L withAD-mix β, the title compound was obtained as a beige solid (7.60 g, 74%yield) after crystallization from ether/EA.

MS (ESI, m/z): 221.1 [M+H⁺].

Z.iii.(R)-2-(tert-butyl-dimethyl-silanyloxy)-1-(3-methoxy-quinoxalin-5-yl)-ethanol

Starting from intermediate Z.ii (7.60 g) and using procedure M, thetitle compound was obtained as a yellow oil (8.80 g, 76% yield).

MS (ESI, m/z): 335.0 [M+H⁺].

Z.iv. (S)-2-amino-2-(3-methoxy-quinoxalin-5-yl)-ethanol

Starting from intermediate Z.iii (8.80 g) and using procedure N, thedesired azide (20 g) was obtained, which was used without furtherpurification in the next reaction. A solution of this azide (20 g,contaminated with PPh₃O) in THF (228 mL) was then treated with PPh₃(7.50 g) and water (4.68 mL). The reaction mixture was further stirredat 50° C. for 2 days, and then extracted with 3M HCl. The aq. phase wasbasified with. aq. NaOH solution and extracted with EA. The org layerwas dried over MgSO₄ and evaporated under reduced pressure, affording ayellow oil (6.10 g; title compound contaminated with traces of PPh₃O).

MS (ESI, m/z): 220.0 [M+H⁺].

Z.v. [(S)-2-hydroxy-1-(3-methoxy-quinoxalin-5-yl)-ethyl]-carbamic acidtert-butyl ester

Starting from intermediate Z.iv (6.00 g) and using procedure G, thetitle compound was obtained as a yellowish foam (5.90 g, 67% yield).

MS (ESI, m/z): 320.1 [M+H⁺].

Z.vi.((S)-3-oxo-5,6-dihydro-3H-pyrrolo[1,2,3-de]quinoxalin-6-yl)-carbamicacid tert-butyl ester

A solution of intermediate Z.v (5.80 g) and TEA (3.0 mL) in DCE (45 mL)was treated dropwise at 0° C. with MsCl (1.55 mL). The reaction mixturewas further refluxed overnight. The reaction mixture was diluted withDCM, washed with water and brine, dried over MgSO₄ and evaporated underreduced pressure affording, after crystallization from ether/EA, a beigesolid (3.50 g; 67% yield) consisting of an inseparable 2:1 mixture ofthe desired product and 4-(3-methoxy-quinoxalin-5-yl)-oxazolidin-2-onewhich was used as such in the next step.

MS (ESI, m/z): 288.0 and 246.0 [M+H⁺].

Z.vii. (S)-6-amino-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from intermediate Z.vi (3.50 g) and using procedure B, thetitle compound was obtained as a beige solid (780 mg, 34% yield). Theside product from cyclisation was removed by acid/base extraction.

MS (ESI, m/z): 188.1 [M+H⁺].

Preparation AA:(R)-6-amino-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

The title compound was prepared in analogy to Preparation Z, usingAD-mix α in the second step.

The analytical data are identical to those of the compound ofPreparation Z.

Preparation AB: rac-methanesulfonic acid4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-ylmethyl ester AB.i.2-(2-methoxy-quinolin-8-yl)-malonic acid dimethyl ester

A mixture of 8-bromo-2-methoxy-quinoline (4.76 g; prepared according toWO 2008/125594) and dimethylmalonate (36 mL) in was degassed by bubblingN₂ through for 10 min and treated with CuBr (3.47 g) and NaOMe (2.6 g).The mixture was heated at 100° C. for 20 h and then partitioned betweenEA and water. The org. phase was washed with brine, dried over MgSO₄ andthe excess dimethylmalonate was removed by distillation. The residue waspurified by CC (Hept/EA 4:1, 2:1), affording an oil (2.80 g; 48% yield).

¹H NMR (CDCl₃) δ: 7.98 (d, J=8.8 Hz, 1H), 7.71 (dd, J=8.2, 1.5 Hz, 1H),7.66 (m, 1H), 7.39 (m, 1H), 6.92 (d, J=8.8 Hz, 1H), 6.00 (s, 1H), 4.03(s, 3H), 3.76 (s, 3H).

AB.ii. 2-(2-methoxy-quinolin-8-yl)-propane-1,3-diol

Starting from intermediate AB.i (5.80 g) and using procedure A, thetitle compound was obtained as a light yellow oil (1.06 g, 23% yield).

MS (ESI, m/z): 234.2 [M+H⁺].

AB.iii. rac-methanesulfonic acid4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-ylmethyl ester

Starting from intermediate AB.ii (840 mg) and using procedure H, butusing 3 eq. of methansulfonyl anhydride instead of MSCl and 4 eq. of Pyras a base, the intermediate dimesylate was further stirred at 70° C. for1 h. The reaction mixture was diluted with 2N HCl and extracted withDCM. The org. phase was dried over MgSO₄ and evaporated under reducedpressure affording, after purification by CC (EE/MeOH 9:1), a beige foam(1.10 g; 76% yield).

MS (ESI, m/z): 280.4 [M+H⁺].

Preparation AC:rac-6-aminomethyl-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one AC.i.(3-methoxy-quinoxalin-5-yl)-acetic acid methyl ester

TBDMSCl (2.4 mL) was added dropwise to a solution of3-methoxy-5-quinoxalineacetonitrile (1.08 g, prepared according to WO2008/126024) in dry MeOH (20 mL). The solution was stirred at refluxovernight. TBDMSCl (2.4 mL) was added and the reaction mixture wasfurther stirred for 8 h. TBDMSCl (2.4 mL) was added and the reactionmixture was further stirred at reflux overnight. The mixture wasconcentrated under reduced pressure and partitioned between EA andwater. The org. layer was washed with 2M NaOH, water and brine, driedover MgSO₄, concentrated under reduced pressure and purified by CC(Hept/EtOAc 1:1), affording a yellow oil (520 mg; 41% yield).

MS (ESI, m/z): 233.3 [M+H⁺].

AC.ii.rac-3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-2-(3-methoxy-quinoxalin-5-yl)-propionicacid methyl ester

A solution of intermediate AC.i (2.03 g) in THF (19 mL) was addeddropwise at −78° C. to a solution of LiHMDS (1M in THF; 10.5 mL) in THF(10 mL). The solution was further stirred at −78° C. stirred for 1 h andtreated dropwise with a solution of N-(bromomethyl)phthalimide (2.6 g)in THF (19 mL). The reaction mixture was further stirred at −78° C. for1 h and at rt overnight. The solution was quenched with 1N HCl (30 mL)and extracted with EA. The org. layer was washed with water and brine,dried over MgSO₄, concentrated under reduced pressure and purified by CC(Hept/EA 1:1), affording, after crystallization from EA, a beige solid(2.28 g; 66% yield).

MS (ESI, m/z): 392.3 [M+H⁺].

AC.iii. rac-3-amino-2-(3-methoxy-quinoxalin-5-yl)-propionic acid methylester

Hydrazine monohydrate (1.42 mL) was added dropwise at rt to a suspensionof intermediate AC.ii (2.28 g) in EtOH (38 mL). After stirring at rt for2 h the solvent was evaporated under reduced pressure and the residuewas taken up in EA and aq. citric acid (10%). The aq. layer was washedwith NH₄OH and extracted with DCM. The org. layer was dried over MgSO₄and evaporated under reduced pressure affording a yellow oil (1.16 g;77% yield) which was further used without any further purification.

MS (ESI, m/z): 262.3 [M+H⁺].

AC.iv.rac-3-tert-butoxycarbonylamino-2-(3-methoxy-quinoxalin-5-yl)-propionicacid methyl ester

Starting from intermediate AC.iii (1.16 g) and using procedure G, thetitle compound was obtained as a colourless solid (1.34 g, 83% yield).

MS (ESI, m/z): 362.0 [M+H⁺].

AC.v.rac-[3-hydroxy-2-(3-methoxy-1,2-dihydro-quinoxalin-5-yl)-propyl]-carbamicacid tert-butyl ester

Starting from intermediate AC.iv (701 mg) and using procedure A, thecompound was obtained as a colourless foam (554 mg, 85% yield).

MS (ESI, m/z): 336.2 [M+H⁺].

AC.vi. rac-[3-hydroxy-2-(3-methoxy-quinoxalin-5-yl)-propyl]-carbamicacid tert-butyl ester

A solution of intermediate AC.v (553 mg) in DCM (30 mL) was treated withMnO₂ (1.35 g). The mixture was stirred at rt for 2 h, filtered andconcentrated in vacuo to give the desired intermediate as a slightlyorange foam (489 mg, 89% yield).

MS (ESI, m/z): 334.1 [M+H⁺].

AC.vii.rac-(3-oxo-5,6-dihydro-3H-pyrrolo[1,2,3-de]quinoxalin-6-ylmethyl)-carbamicacid tert-butyl ester

Starting from intermediate AC.vi (486 mg) and using procedure H, thetitle compound was obtained as a beige solid (393 mg, 89% yield).

MS (ESI, m/z): 302.1 [M+H⁺].

AC.viii. rac-6-aminomethyl-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from intermediate AC.viii (388 mg) and using procedure B, thetitle compound was obtained as a yellow solid (172 mg, 66% yield).

MS (ESI, m/z): 202.3 [M+H⁺].

Preparation AD:(S)-6-amino-7-fluoro-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one AD.i.(R)-1-(6-fluoro-3-methoxy-quinoxalin-5-yl)-ethane-1,2-diol

Starting from 7-fluoro-2-methoxy-8-(2-propen-1-yl)-quinoxaline (3.24 g;prepared according to WO 2008/003690) and using procedure L with AD-mixβ, the title compound was obtained, after purification by CC (Hept/EA1:1 then 0:1), as a beige solid (3.39 g, 90% yield).

¹H NMR (DMSO d6) δ: 8.57 (s, 1H), 7.96 (dd, J=9.1, 5.6 Hz, 1H), 7.48(dd, J=10.3, 9.1 Hz, 1H), 5.64 (d, J=6.7 Hz, 1H), 5.26 (d, J=6.4 Hz,1H), 4.75 (m, 1H), 4.05 (s, 3H), 3.88 (m, 1H), 3.73 (m, 1H).

AD.ii.(R)-2-(tert-butyl-dimethyl-silanyloxy)-1-(6-fluoro-3-methoxy-quinoxalin-5-yl)-ethanol

Starting from intermediate AD.i (3.39 g) and using procedure M, thetitle compound was obtained as a colourless oil (4.83 g, 96% yield).

¹H NMR (CDCl₃) δ: 8.47 (s, 1H), 7.95 (m, 1H), 7.35 (m, 1H), 5.5 (m, 1H),4.09 (s, 3H), 4.03 (m, 2H), 0.76 (s, 9H), −0.12 (d, J=5.0 Hz, 6H).

AD.iii.(S)-[2-(tert-butyl-dimethyl-silanyloxy)-1-(6-fluoro-3-methoxy-quinoxalin-5-yl)-ethyl]-carbamicacid tert-butyl ester

Starting from intermediate AD.ii (4.73 g) and using procedure N′, thetitle compound was obtained, after purification by CC (Hept/EA 4:1), asa colourless foam (3.48 g; 84% yield).

¹H NMR (CDCl₃) δ: 8.45 (s, 1H), 7.93 (dd, J=9.1, 5.6 Hz, 1H), 7.30 (m,1H), 6.60 (m, 1H), 5.85 (m, 1H), 4.12 (s, 4H), 3.94 (m, 2H), 1.43 (s,9H), 0.75 (s, 9H), −0.08 (s, 3H), −0.12 (s, 3H).

AD.iv.(S)-[1-(6-fluoro-3-methoxy-quinoxalin-5-yl)-2-hydroxy-ethyl]-carbamicacid tert-butyl ester

Starting from intermediate AD.iii (5.54 g) and using procedure J, thetitle compound was obtained as a colourless foam (3.48 g, 84% yield).

¹H NMR (CDCl₃) δ: 8.45 (s, 1H), 7.95 (dd, J=9.4, 5.9 Hz, 1H), 7.34 (m,1H), 6.60 (m, 1H), 5.85 (m, 1H), 4.11 (s, 3H), 3.92 (m, 2H), 1.42 (s,9H).

AD.v. (S)-(7-fluoro-3-oxo-5,6-dihydro-3H-pyrrolo[1, 2,3-de]quinoxalin-6-yl)-carbamic acid tert-butyl ester

Starting from intermediate AD.iv (3.45 g) and using procedure H followedby heating at reflux for 12 h, a foam (2.64 g) was obtained whichcontained the desired product in a 1:1 mixture with(S)-4-(6-fluoro-3-methoxy-quinoxalin-5-yl)-oxazolidin-2-one. It was usedas such in the next step.

AD.vi.(S)-6-amino-7-fluoro-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from the mixture obtained at step AD.v (2.64 g, purity 50%) andusing procedure B followed by acid/base extraction, the title compoundwas obtained as an orange solid (550 mg, 60% yield).

¹H NMR (DMSO d6) δ: 8.12 (s, 1H), 7.74 (dd, J=8.8, 4.4 Hz, 1H), 7.11 (m,1H), 4.94 (dd, J=8.5, 3.8 Hz, 1H), 4.50 (dd, J=13.2, 8.5 Hz, 1H), 3.90(dd, J=13.2, 3.8 Hz, 1H), 2.32 (br., 2H).

Preparation AE:rac-1-aminomethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one AE.i.rac-1-azidomethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

A solution of the compound of Preparation AB (1.00 g) in DMF (16 mL) washeated at 60° C. for 3 h in presence of NaN₃ (2.80 g). The reactionmixture was diluted with water and extracted with EA. The org. layer waswashed with water and brine, dried over MgSO₄ and evaporated affording ayellow powder (800 mg; 99% yield).

¹H NMR (CDCl₃) δ: 7.72 (d, J=9.4 Hz, 1H), 7.45 (m, 2H), 7.19 (m, 1H),6.69 (d, J=9.4 Hz, 1H), 4.55 (dd, J=13.2, 9.4 Hz, 1H), 4.26 (dd, J=13.2,4.7 Hz, 1H), 3.91 (m, 1H), 3.67 (m, 2H).

AE.ii. rac-1-aminomethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from intermediate AE.i (800 mg) and using procedure F, thetitle compound was obtained as a yellow oil (310 mg, 44% yield).

¹H NMR (CDCl₃) δ: 7.70 (d, J=9.4 Hz, 1H), 7.41 (m, 2H), 7.17 (t, J=7.6Hz, 1H), 6.67 (d, J=9.4 Hz, 1H), 4.54 (dd, J=13.2, 9.7 Hz, 1H), 4.32(dd, J=12.6, 4.7 Hz, 1H), 3.80 (m, 1H), 3.10 (d, J=6.2 Hz, 2H).

Preparation AF:6-[(R)-5-(2-amino-ethyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-oneAF.i.6-[(R)-5-(2-azido-ethyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-one

A solution of the compound of Preparation J (2.5 g) and NaN₃ (523 mg) inDMF (12 mL) was heated at 80° C. overnight. The reaction mixture wasdiluted with EA and extracted with water and brine. The org. layer wasdried over MgSO₄ and evaporated under reduced pressure. The residue wasstirred in ether/MeOH, affording a beige solid (1.9 g; 89% yield).

MS (ESI, m/z): 320.2 [M+H⁺].

AF.ii.6-[(R)-5-(2-amino-ethyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-one

Starting from intermediate AF.i (1.8 g) and using procedure F, the titlecompound was obtained as a colourless solid (1.40 g, 85% yield).

MS (ESI, m/z): 294.4 [M+H⁺].

Preparation AG: methanesulfonic acid(S)-2-oxo-3-(4-propyl-phenyl)-oxazolidin-5-ylmethyl ester AG.i.(S)-5-hydroxymethyl-3-(4-propyl-phenyl)-oxazolidin-2-one

Starting from 4-propyl-aniline and following the procedure described forthe preparation of intermediate R.i., the title compound was obtained asa yellow solid (4.3 g; 63% yield)

MS (ESI, m/z): 235.9 [M+H⁺].

AG.ii. Methanesulfonic acid(S)-2-oxo-3-(4-propyl-phenyl)-oxazolidin-5-ylmethyl ester

Starting from intermediate AG.i (4.25 g) and using procedure H (withhowever 1.5 eq. Ms₂O instead of MsCl), the title compound was obtainedas an off-white solid (4.30 g, 76% yield).

MS (ESI, m/z): 314.1 [M+H⁺].

Preparation AH: methanesulfonic acid(S)-3-(4-butyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl ester AH.i.(S)-5-hydroxymethyl-3-(4-butyl-butyl)-oxazolidin-2-one

Starting from 4-butyl-aniline and following the procedure described forthe preparation of intermediate R.i, the title compound was obtained asa yellow solid (2.99 g; 58% yield).

¹H NMR (CDCl₃) δ: 7.43 (d, J=8.8 Hz, 2H), 7.17 (d, J=8.8 Hz, 2H), 4.73(m, 1H), 3.99 (m, 3H), 3.76 (m, 1H), 2.58 (m, 2H), 2.00 (br. s, 1H),1.57 (m, 2H), 1.34 (m, 2H), 0.92 (t, J=7.0 Hz, 3H).

AH.ii. Methanesulfonic acid(S)-3-(4-butyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl ester

Starting from intermediate AH.i (2.90 g) and using procedure H (withhowever 1.5 eq. of Ms₂O instead of MsCl), the title compound wasobtained as an off-white solid (2.48 g, 65% yield).

MS (ESI, m/z): 328.3 [M+H⁺].

Preparation AI: methanesulfonic acid2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylester

The title compound was prepared in analogy to Preparation J, usinghowever tert-butyl-dimethyl-[(S)-2-oxiranyl-ethoxy]-silane.

The analytical data were identical with those of the compound ofPreparation J.

Preparation AJ: methanesulfonic acid2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylester AJ.i. (2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)-carbamic acidtert-butyl ester

A suspension of 2,3-dihydro-1,4-dioxino[2,3-c]pyridine-7-carboxylic acid(3.20 g; prepared according to WO 2007/016610) in tBuOH (100 mL) wastreated with DPPA (4.60 mL) and TEA (3.0 mL) and heated at 80° C.overnight. The solvent was evaporated under reduced pressure and theresidue as partitioned between water and EA. The org. layer was washedwith brine, dried over MgSO₄ and evaporated under reduced pressure. Theresidue was stirred in ether, affording a beige solid (2.90 g; 65%yield).

¹H NMR (CDCl₃) δ: 7.84 (s, 1H), 7.49 (s, 1H), 4.31 (m, 2H), 4.23 (m,2H), 1.52 (s, 11H).

AJ.ii.rac-5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-3-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)-oxazolidin-2-one

A solution of intermediate AJ.i (3.30 g) and2-[2-[[(tert-butyl)dimethylsilyl]oxy]ethyl]-oxirane (2.65 g; preparedaccording to J. Org. Chem. (2008), 73(3), 1093-1098) in DMF (42 mL) wascooled to 0° C. and treated with tBuOLi (18 mL; 2.2M in THF). Thereaction mixture was allowed to reach rt and further stirred at 80° C.for 2 days. The reaction mixture was diluted with EA and washed withwater and brine. The org. layer was dried over MgSO₄ and purified by CC(Hex/EA1:1), affording a yellow oil (2.70 g; 54% yield).

MS (ESI, m/z): 381.0 [M+H⁺].

AJ.iii.rac-3-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)-5-(2-hydroxy-ethyl)-oxazolidin-2-one

Starting from intermediate AJ.ii and using procedure J, the titlecompound was obtained as a yellow solid (1.10 g, 58% yield).

MS (ESI, m/z): 267.1 [M+H⁺].

AJ.iv. Methanesulfonic acid2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylester

Starting from intermediate AJ.iii and using procedure H, the titlecompound was obtained as a beige solid (1.30 g, 100% yield).

MS (ESI, m/z): 345.2 [M+H⁺].

Preparation AK: rac-methanesulfonic acid2-[3-(2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-6-yl)-2-oxo-oxazolidin-5-yl]-ethylester AK.i. (2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-6-yl)-carbamic acidbenzyl ester

A solution of 2,3-dihydro-1,4-dioxino[2,3-b]pyridin-6-amine (commercial;2.70 g) in acetone/water 1:1 (40 mL) was treated at 0° C. with 1M NaHCO₃(35 mL) and CbzCl (2.63 mL). The reaction mixture was stirred at rt for3 h, the org. solvent was evaporated under reduced pressure and theresidue was partitioned between water and ether/EA. The org layer wasdried over MgSO₄ and evaporated under reduced pressure, affording abeige solid (5.3 g; 100% yield).

¹H NMR (CDCl₃) δ: 7.50 (d, J=8.5 Hz, 1H), 7.36 (m, 5H), 7.20 (d, J=8.8Hz, 1H), 7.15 (br., 1H), 4.37 (m, 2H), 4.19 (m, 2H).

AK.ii.rac-5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-3-(2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-6-yl)-oxazolidin-2-one

Starting from intermediate AK.i and2-[2-[[(tert-butyl)dimethylsilyl]oxy]ethyl]-oxirane, the compound wasprepared in analogy to Preparation AJ, step AJ.ii. The product waspurified by CC (Hex/EA 1:1), affording a brown oil (2.90 g; 73% yield).

MS (ESI, m/z): 381.2 [M+H⁺].

AK.iii.rac-3-(2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-6-yl)-5-(2-hydroxy-ethyl)-oxazolidin-2-one

Starting from intermediate AK.ii and using procedure J, the titlecompound was obtained as a yellow solid (1.10 g, 56% yield).

MS (ESI, m/z): 266.8 [M+H⁺].

AK.iv. rac-methanesulfonic acid2-[3-(2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-6-yl)-2-oxo-oxazolidin-5-yl]-ethylester

Starting from intermediate AK.iii and using procedure H, the titlecompound was obtained as a beige solid (1.24 g, 96% yield).

¹H NMR (CDCl₃) δ: 7.71 (d, J=8.8 Hz, 1H), 7.24 (m, 1H), 4.79 (m, 1H),4.43 (m, 4H), 4.33 (m, 1H), 4.23 (m, 2H), 3.89 (dd, J=10.3, 6.7 Hz, 1H),3.04 (s, 3H), 2.20 (m, 2H).

Preparation AL: methanesulfonic acid2-[(R)-3-(4-ethoxy-phenyl)-2-oxo-oxazolidin-5-yl]-ethyl ester AL.i.(R)-4-(tert-butyl-dimethyl-silanyloxy)-1-(4-ethoxy-phenylamino)-butan-2-ol

A solution of 4-ethoxy-aniline (commercial; 3.2 mL) in EtOH/water (9:1;150 mL) was reacted with(2R)-2-[2-[[(tert-butyl)dimethylsilyl]oxy]ethyl]-oxirane (preparedaccording to WO 2007/144423) and further heated at 80° C. overnight. Thesolvents were removed under reduced pressure and the residue waspurified by CC (EA/Hept 1:1), affording a brown oil (5.22 g; 62% yield).

MS (ESI, m/z): 340.2 [M+H⁺].

AL.ii.(R)-5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-3-(4-ethoxy-phenyl)-oxazolidin-2-one

Starting from intermediate AL.i and using procedure I, the titlecompound was obtained as an off-white solid (4.30 g, 76% yield).

MS (ESI, m/z): 366.1 [M+H⁺].

AL.iii. (R)-3-(4-ethoxy-phenyl)-5-(2-hydroxy-ethyl)-oxazolidin-2-one

Starting from intermediate AL.ii and using procedure J, the titlecompound was obtained as an off-white solid (1.53 g, 52% yield).

MS (ESI, m/z): 251.9 [M+H⁺].

AL.iv. Methanesulfonic acid2-[(R)-3-(4-ethoxy-phenyl)-2-oxo-oxazolidin-5-yl]-ethyl ester

Starting from intermediate AL.iii and using procedure H, the titlecompound was obtained as an off-white solid (1.89 g, 96% yield).

MS (ESI, m/z): 330.0 [M+H⁺].

Preparation AM: methanesulfonic acid2-[(R)-2-oxo-3-(4-propyl-phenyl)-oxazolidin-5-yl]-ethyl ester AM.i.(R)-4-(tert-butyl-dimethyl-silanyloxy)-1-(4-propyl-phenylamino)-butan-2-ol

Starting from 4-propyl-aniline, the title compound was prepared inanalogy to Preparation AL, step AL.i. A brown oil (6.99 g; 84% yield)was obtained.

MS (ESI, m/z): 338.2 [M+H⁺].

AM.ii.(R)-5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-3-(4-propyl-phenyl)-oxazolidin-2-one

Starting from intermediate AM.i and using procedure I, the titlecompound was obtained as a brown oil (4.50 g, 60% yield).

MS (ESI, m/z): 364.1 [M+H⁺].

AM.iii. (R)-5-(2-hydroxy-ethyl)-3-(4-propyl-phenyl)-oxazolidin-2-one

Starting from intermediate AM.ii and using procedure J, the titlecompound was obtained as a yellowish solid (1.76 g, 57% yield).

MS (ESI, m/z): 249.9 [M+H⁺].

AM.iv. Methanesulfonic acid2-[(R)-2-oxo-3-(4-propyl-phenyl)-oxazolidin-5-yl]-ethyl ester

Starting from intermediate AM.iii and using procedure H, the titlecompound was obtained as an off-white solid (2.13 g, 93% yield).

MS (ESI, m/z): 328.4 [M+H⁺].

Preparation AN: methanesulfonic acid2-[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-yl]-ethylester AN.i.(R)-4-(tert-butyl-dimethyl-silanyloxy)-1-(2,3-dihydro-benzo[1,4]dioxin-6-ylamino)-butan-2-ol

Starting from 2,3-dihydro-1,4-benzodioxin-6-amine (commercial), thetitle compound was prepared in analogy to Preparation AL, step AL.i. Abrown oil (4.50 g; 51% yield) was obtained.

MS (ESI, m/z): 354.3 [M+H⁺].

AN.ii.(R)-5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-oxazolidin-2-one

Starting from intermediate AN.i and using procedure I, the titlecompound was obtained as a yellow solid (3.42 g, 71% yield).

MS (ESI, m/z): 380.2 [M+H⁺].

AN.iii.(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-5-(2-hydroxy-ethyl)-oxazolidin-2-one

Starting from intermediate AN.ii and using procedure J, the titlecompound was obtained as an off-white solid (1.72 g, 72% yield).

¹H NMR (CDCl₃) δ: 7.06 (d, J=2.6 Hz, 1H), 6.97 (dd, J=8.8, 2.6 Hz, 1H),6.84 (m, 1H), 4.81 (m, 1H), 4.24 (m, 4H), 4.06 (t, J=8.8 Hz, 1H), 3.88(m, 2H), 3.69 (dd, J=8.8, 7.3 Hz, 1H), 2.03 (m, 2H), 1.82 (br. s, 1H).

AN.iv. Methanesulfonic acid2-[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-yl]-ethylester

Starting from intermediate AN.iii and using procedure H, the titlecompound was obtained as an off-white solid (2.03 g, 92% yield).

MS (ESI, m/z): 344.2 [M+H⁺].

Preparation AO: rac-methanesulfonic acid2-{3-[4-(4-methoxy-benzyl)-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl]-2-oxo-oxazolidin-5-yl}-ethylester AO.i.6-bromo-4-(4-methoxy-benzyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one

A suspension of 6-bromo-2H-pyrido[3,2-b]-1,4-oxazin-3(4H)-one (2.0 g;prepared according to WO 01/30782) in DMF (40 mL) was treated with4-methoxybenzyl chloride (1.18 mL) and Cs₂CO₃ (8.5 g) and stirred at rtfor 2 h. The solvent was evaporated under reduced pressure and theresidue was partitioned between EA and water. The org. layer was washedwith brine, dried over MgSO₄ and evaporated under reduced pressure. Theresidue was triturated with Hept, affording a beige solid (2.8 g; 92%yield).

¹H NMR (CDCl₃) δ: 7.49 (d, J=8.8 Hz, 2H), 7.05 (s, 2H), 6.83 (d, J=8.8Hz, 2H), 6.83 (d, J=8.8 Hz, 2H), 6.83 (d, J=8.8 Hz, 2H), 4.67 (s, 2H),3.77 (s, 3H).

AO.ii. rac-1-azido-4-(tert-butyl-dimethyl-silanyloxy)-butan-2-ol

A solution of 2-[2-[[(tert-butyl)dimethylsilyl]oxy]ethyl]-oxirane (5.0g; prepared according to WO 2007/144423) in MeOH (150 mL) was reactedwith NaN₃ (3.95 g) and NH₄Cl (2.37 g). The reaction mixture was furtherstirred at 80° C. overnight. The solvent was evaporated under reducedpressure and the residue was partitioned between EA and water. The org.layer was washed with brine, dried over Na₂SO₄ and evaporated underreduced pressure, affording a yellow oil (4.9 g; 81% yield).

¹H NMR (CDCl₃) δ: 4.01 (m, 1H), 3.87 (m, 2H), 3.30 (m, 2H), 1.72 (m,2H), 0.90 (m, 9H), 0.06 (m, 6H).

AO.iii. rac-1-amino-4-(tert-butyl-dimethyl-silanyloxy)-butan-2-ol

A solution of intermediate AO.ii (4.85 g) in THF (100 mL) washydrogenated for 3 h over 10% Pd/C (1.0 g). The catalyst was filteredoff and the filtrate was evaporated under reduced pressure, affording ayellow oil (4.1 g; 94.5% yield).

MS (ESI, m/z): 219.8 [M+H⁺].

AO.iv. rac-5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-oxazolidin-2-one

Starting from intermediate AO.iii (4.0 g) and using procedure I, thetitle compound was obtained as a light yellow oil (3.3 g; 74% yield).

¹H NMR (CDCl₃) δ: 5.22 (br., 1H), 4.80 (m, 1H), 3.74 (m, 3H), 3.33 (m,1H), 1.93 (m, 2H), 0.89 (m, 9H), 0.07 (m, 6H).

AO.v.rac-6-{5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-oxo-oxazolidin-3-yl}-4-(4-methoxy-benzyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one

Intermediates AO.iv (1.97 g) and AO.i (2.8 g), CuI (305 mg) and K₂CO₃(2.2 g) were placed in a round bottom flask which was then flushed withargon. Trans-1,2-diaminocyclohexane (1.2 mL) and dioxane (60 mL) wereadded to the mixture and the reaction flask was again flushed withargon. The reaction mixture was stirred at 100° C. for 2 days andpartitioned between EA and water. The org. layer was washed with brine,dried over MgSO₄ and evaporated under reduced pressure. The residue waspurified by CC (DCM/MeOH 19:1), affording, after crystallisation fromHept, a colourless solid (1.7 g; 41% yield).

¹H NMR (CDCl₃) δ: 7.81 (d, J=8.8 Hz, 1H), 7.28 (m, 3H), 6.81 (m, 2H),5.20 (s, 2H), 4.82 (m, 1H), 4.28 (m, 1H), 3.85 (m, 3H), 3.77 (s, 3H),2.00 (m, 2H), 0.89 (s, 9H), 0.07 (s, 6H).

AO.vi.rac-6-[5-(2-hydroxy-ethyl)-2-oxo-oxazolidin-3-yl]-4-(4-methoxy-benzyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one

Starting from intermediate AO.v (1.7 g) and using procedure J, the titlecompound was obtained, after purification by CC (EA then EA/MeOH 9:1),as a yellow oil (1.4 g; 100% yield).

MS (ESI, m/z): 400.0 [M+H⁺].

AO.vii. rac-methanesulfonic acid2-{3-[4-(4-methoxy-benzyl)-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl]-2-oxo-oxazolidin-5-yl}-ethylester

Starting from intermediate AO.vi (1.32 g) and using procedure H, thetitle compound was obtained as a colourless foam (1.3 g; 82.5% yield)

MS (ESI, m/z): 477.8 [M+H⁺].

Preparation AP:6-[(S)-5-(2-amino-ethyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-oneAP.i.6-[(S)-5-(2-azido-ethyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-one

A solution of intermediate L (1.90 g) in DMF (8 mL) was treated withNaN₃ (400 mg) and stirred at 80° C. overnight. The reaction mixture wasdiluted with water and extracted with EA. The org. layer was washed withwater and brine, dried over MgSO₄ and evaporated under reduced pressure.The residue was stirred in ether/MeOH, affording a beige solid (1.30 g;80% yield).

MS (ESI, m/z): 320.3 [M+H⁺].

AP.ii.6-[(S)-5-(2-amino-ethyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-one

Starting from intermediate AP.i and using procedure F, the titlecompound was obtained as a beige solid (0.90 g, 82% yield).

MS (ESI, m/z): 294.4 [M+H⁺].

Preparation AQ: methanesulfonic acid2-[(S)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-yl]-ethylester

Starting from (2S)-2-[2-[[(tert-butyl)dimethylsilyl]oxy]ethyl]-oxirane,the title compound was prepared in analogy to Preparation AN.

The analytical data were identical with those of the compound ofPreparation AN.

Preparation AR:3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propionaldehydeAR.i. (R)-1-azido-5-(tert-butyl-dimethyl-silanyloxy)-pentan-2-ol

Starting from (R)-2-[2-[[(tert-butyl)dimethylsilyl]oxy]propyl]-oxirane(5.0 g; prepared according to Organic Letters (2005), 7(18), 3997-4000)and NaN₃, the title compound was prepared in analogy to Preparation AO,step AO.ii. It was obtained as an oil (5.17 g; 86% yield).

¹H NMR (CDCl₃) δ: 3.79 (m, 1H), 3.68 (m, 2H), 3.29 (m, 2H), 1.66 (m,4H), 0.90 (m, 9H), 0.07 (m, 6H).

AR.ii.(R)-5-[2-(tert-butyl-dimethyl-silanyloxy)-propyl]-oxazolidin-2-one

The title compound was prepared in analogy to Preparation AO, stepsAO.iii and AO.iv by hydrogenation of intermediate AR.ii using procedureF and reaction with CDI using procedure I. It was obtained as acolourless solid (3.48 g; 67% yield).

¹H NMR (CDCl₃) δ: 5.22 (br., 1H), 4.68 (m, 1H), 3.66 (m, 3H), 3.25 (t,J=7.6 Hz, 1H), 1.72 (m, 4H), 0.89 (m, 9H), 0.05 (m, 6H).

AR.iii.(R)-6-{5-[2-(tert-butyl-dimethyl-silanyloxy)-propyl]-2-oxo-oxazolidin-3-yl}-4-(4-methoxy-benzyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one

Starting from intermediates AO.i (1.97 g) and AR.ii, the title compoundwas prepared in analogy to Preparation AO, step AO.v. It was obtained asa colourless foam (4.43 g; 70% yield).

¹H NMR (CDCl₃) δ: 7.80 (d, J=8.5 Hz, 1H), 7.28 (m, 3H), 6.81 (d, J=8.8Hz, 2H), 5.20 (s, 2H), 4.67 (m, 3H), 4.22 (dd, J=10.0, 8.5 Hz, 1H), 3.77(s, 3H), 3.70 (m, 2H), 1.78 (m, 4H), 0.90 (m, 9H), 0.06 (s, 6H).

AR.iv.(R)-6-[5-(2-hydroxy-propyl)-2-oxo-oxazolidin-3-yl]-4-(4-methoxy-benzyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one

The title compound was prepared in analogy to Preparation AO, stepAO.vi, starting from intermediate AR.iii. It was obtained as acolourless solid (640 mg; 38% yield).

¹H NMR (DMSO d6) δ: 11.16 (s, 1H), 7.57 (m, 1H), 7.40 (d, J=8.8 Hz, 1H),4.68 (s, 1H), 4.59 (s, 2H), 4.47 (t, J=5.0 Hz, 1H), 4.19 (m, 1H), 3.69(dd, J=10.0, 7.0 Hz, 1H), 3.43 (q, J=6.2 Hz, 2H), 1.73 (m, 2H), 1.51(dd, J=9.7, 6.7 Hz, 2H).

AR.v.3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propionaldehyde

A solution of SO₃.Pyr complex (900 mg) in DMSO (3 mL) was added dropwiseat rt over 10 min to a suspension of intermediate AR.iv (830 mg) andDIPEA (1.45 mL) in DCM/DMSO (1:1; 5 mL). The mixture was further stirredat rt for 1 h, diluted with water and extracted with DCM. The org. layerwas successively washed with water and brine, dried over MgSO₄,concentrated under reduced pressure and crystallized from ether/EA,affording a colourless solid (618 mg; 75% yield).

¹H NMR (DMSO d6) δ: 11.17 (s, 1H), 9.68 (s, 1H), 7.57 (m, 1H), 7.40 (d,J=8.8 Hz, 1H), 4.66 (m, 1H), 4.59 (s, 2H), 4.20 (m, 1H), 3.70 (dd,J=10.0, 7.0 Hz, 1H), 2.59 (m, 2H), 1.98 (m, 2H).

Preparation AS: (S)-1-amino-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-oneAS.i. 2-methoxy-8-vinyl-quinoline

(PPh₃)₄Pd (578 mg) was added at rt to a solution of vinylboronicanhydride pyridine complex (1.2 g) in DME (80 mL). The solution wasdegassed by bubbling N₂ through for 20 min. K₂CO₃ (1.38 g), water (24mL) and trifluoro-methanesulfonic acid 2-methoxy-quinolin-8-yl ester(3.07 g) were added. The mixture was refluxed overnight, cooled to rtand partitioned between water and ether. The aq. phase was washed withether and the combined org. phases were washed with water and brine,dried over MgSO₄, concentrated under reduced pressure and purified by CC(Hept/EA 4:1), affording a yellow liquid (1.18 g; 64% yield).

¹H NMR (CDCl₃) δ: 7.97 (d, J=8.8 Hz, 1H), 7.88 (m, 2H), 7.64 (dd, J=7.9,1.5 Hz, 1H), 7.36 (t, J=7.6 Hz, 1H), 6.91 (d, J=8.8 Hz, 1H), 6.02 (dd,J=17.9, 1.8 Hz, 1H), 5.45 (dd, J=11.1, 1.8 Hz, 1H), 4.10 (s, 3H).

AS.ii. (R)-1-(2-methoxy-quinolin-8-yl)-ethane-1,2-diol

Starting from intermediate AS.i and AD-mix β and using procedure L, thetitle compound was obtained as a beige solid (3.22 g, quant).

MS (ESI, m/z): 279.3 [M+H⁺].

AS.iii.(R)-2-(tert-butyl-dimethyl-silanyloxy)-1-(2-methoxy-quinolin-8-yl)-ethanol

Starting from intermediate AS. ii and using procedure M, the titlecompound was obtained as a yellow oil (4.16 g, quant.).

MS (ESI, m/z): 334.0 [M+H⁺].

AS.iv.[(S)-2-(tert-butyl-dimethyl-silanyloxy)-1-(2-methoxy-quinolin-8-yl)-ethyl]-carbamicacid tert-butyl ester

Starting from intermediate AS.iii (4.70 g), the title compound wasprepared in analogy to Preparation Z, steps Z.iv (Mitsunobu reactionfollowed by azide reduction) and Z.v. (Boc protection using procedureG). It was obtained as a slightly yellow oil (8.4 g; quant.;contaminated by Boc₂O).

MS (ESI, m/z): 359.3 [M+H⁺].

AS.v. [(S)-2-hydroxy-1-(2-methoxy-quinolin-8-yl)-ethyl]-carbamic acidtert-butyl ester

Starting from intermediate AS.iv (6.48 g) and using procedure J, thetitle compound was obtained as a colourless foam (2.99 g; 63% yield).

MS (ESI, m/z): 319.0 [M+H⁺].

AS.vi.((S)-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamic acidtert-butyl ester

Starting from intermediate AS.v (3.34 g) and using procedure H (butheating the reaction mixture at 50° C.), the title compound was obtainedas a colourless solid (2.64 g; 88% yield).

MS (ESI, m/z): 287.1 [M+H⁺].

AS.vii. (S)-1-amino-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from intermediate AS.vi (2.63 g) and using procedure B, thetitle compound was obtained as a colourless solid (1.58 g; 93% yield).

MS (ESI, m/z): 187.1 [M+H⁺].

Preparation AT:(S)-4-aminomethyl-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-oneAT.i. Acetic acid(S)-3-azido-2-(6-methoxy-[1,5]naphthyridin-4-yl)-propyl ester

Starting from intermediate V.ii (1.65 g) and using the same procedure asfor the preparation of intermediate Z.iv, the title compound wasobtained as a colourless oil (1.63 g; 90% yield).

MS (ESI, m/z): 302.0 [M+H⁺].

AT.ii. Acetic acid(S)-3-tert-butoxycarbonylamino-2-(6-methoxy-[1,5]naphthyridin-4-yl)-propylester

Starting from intermediate AT.i (1.63 g) and using successivelyprocedures F and G, the title compound was obtained as pale yellow oil(2.04 g; 100% yield).

MS (ESI, m/z): 376.2 [M+H⁺].

AT.iii.[(S)-3-hydroxy-2-(6-methoxy-[1,5]naphthyridin-4-yl)-propyl]-carbamicacid tert-butyl ester

A suspension of intermediate AT.ii (2.05 g) and K₂CO₃ (3.02 g) in MeOH(72 mL) was stirred at rt for 30 min. The solvent was removed underreduced pressure and the residue was taken up in DCM/water. The org.layer was washed with brine, dried over MgSO₄, concentrated and purifiedby CC (DCM/MeOH/NH₄OH 1000:50:4), affording a colourless foam (1.28 g;70% yield).

MS (ESI, m/z): 334.2 [M+H⁺].

AT.iv.((S)-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de][1,5]naphthyridin-4-ylmethyl)-carbamicacid tert-butyl ester

Starting from intermediate AT.iii (1.28 g) and using procedure H for theformation of the mesylate, followed by heating of the reaction mixturefor 2 h at 60° C. to complete the cyclisation, the title compound wasobtained as a colourless foam (985 mg; 85% yield).

MS (ESI, m/z): 302.2 [M+H⁺].

AT.v.(S)-4-aminomethyl-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from intermediate AT.iv (980 mg) and using procedure B, thetitle compound was obtained as pale yellow solid (522 mg; 80% yield).

MS (ESI, m/z): 202.2 [M+H⁺].

Preparation AU:3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propionaldehyde

Starting from (S)-tert-butyl-dimethyl-(3-oxiranyl-propoxy)-silane(prepared according to Org. Lett. (2005), 7(19), 4083-4086), the titlecompound (obtained as a pink solid) was prepared in analogy toPreparation U in 4 steps (epoxide opening: 50% yield; oxazolidinoneformation: 100% yield; alcohol deprotection: 71% yield; aldehydeformation: 91% yield).

The analytical data were identical with those of the compound ofPreparation U.

Preparation AV:3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propionaldehyde

Starting from (S)-tert-butyl-dimethyl-(3-oxiranyl-propoxy)-silane(prepared according to Org. Lett. (2005), 7(19), 4083-4086), the titlecompound (obtained as a beige solid) was prepared in analogy toPreparation T in 4 steps (epoxide opening: 45% yield, oxazolidinoneformation: 100% yield, alcohol deprotection: 65% yield, aldehydeformation: 87% yield).

The analytical data were identical with those of the compound ofPreparation T.

Preparation AW: methanesulfonic acid3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylester AW.i.6-[(S)-5-(tert-butyl-dimethyl-silanyloxy)-2-hydroxy-pentylamino]-4H-benzo[1,4]thiazin-3-one

A mixture of (S)-tert-butyl-dimethyl-(3-oxiranyl-propoxy)-silane (28.3g, prepared according to Org. Lett. (2005), 7, 3997) and6-amino-4H-benzo[1,4]thiazin-3-one (23.6 g) in MeCN (390 mL) was treatedwith LiClO₄ (41.8 g) and heated at 60° C. for 4 h. The volatiles wereremoved under reduced pressure and the residue partitioned between EAand brine. The org. phase was dried over MgSO₄ and concentrated. Theresidue was purified by CC (Hept/EA 1:1, EA) to give the desiredintermediate as a yellowish foam (8.4 g; 16% yield).

MS (ESI, m/z): 397.1 [M+H⁺].

AW.ii.6-{(S)-5-[3-(tert-butyl-dimethyl-silanyloxy)-propyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one

A solution of intermediate AW.i (8.0 g) in THF (500 mL) was treated withCDI (4.9 g) and heated at 50° C. overnight. The mixture was cooled tort, diluted with EA and washed with water and brine, dried over MgSO₄and concentrated. The product was crystallized from Hept/EA to give thedesired oxazolidinone as a beige solid (4.5 g; 53% yield).

MS (ESI, m/z): 423.4 [M+H⁺].

AW.iii.6-[(S)-5-(3-hydroxy-propyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-one

A suspension of intermediate AW.ii (4.5 g) in THF (42 mL) was treatedwith 1M TBAF solution in THF (1 eq.). The brown solution was stirred atrt for 4 h, diluted with EA and washed with water and brine, dried overMgSO₄ and concentrated. The residue was purified by CC (EA then EA/MeOH9:1) to give the desired alcohol as a yellowish foam (3.6 g; 100%yield).

MS (ESI, m/z): 309.3 [M+H⁺].

AW.iv. Methanesulfonic acid3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylester

A suspension of intermediate AW.iii (3.0 g) in DCM was treated with TEA(2.8 mL) and dropwise with MsCl (1.37 g). The mixture was stirred at rtfor 2 h, diluted with DCM, washed with water, dried over MgSO₄ andconcentrated. The residue was crystallized from ether/EA to give thedesired mesylate as a beige solid (3.6 g; 93% yield).

MS (ESI, m/z): 387.2 [M+H⁺].

Preparation AX:rac-4-amino-3-fluoro-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-oneAX.i. 7-fluoro-2-methoxy-8-vinyl-[1,5]naphthyridine

To a solution of 8-bromo-7-fluoro-2-methoxy-1,5-naphthyridine (5.0 g;commercial) in 1,2-DME (150 mL) was added tetrakis-(PPh₃)Pd (1.1 g) andthe mixture was purged with N₂ for 20 min. K₂CO₃ (2.69 g), water (50 mL)and vinylboronic anhydride pyridine complex (2.34 g) were added. Themixture was stirred at reflux for 3 h. After cooling to rt, water wasadded and the mixture was extracted with EA. The combined org. phaseswere washed with brine, dried over MgSO₄, concentrated and purified byCC (EA/Hept 1:1), affording the title intermediate as a brown oil (3.12g, 79% yield).

MS (ESI, m/z): 205.0 [M+H⁺].

AX.ii. (R)-1-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-ethane-1,2-diol

Starting from intermediate AX.i (3.12 g) and using procedure L withAD-mix (3, the title compound was obtained as an off-white solid (4 g,quant.).

MS (ESI, m/z): 239.0 [M+H⁺].

AX.iii.(R)-2-(tert-butyl-dimethyl-silanyloxy)-1-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-ethanol

To a solution of intermediate AX.ii (3.96 g) in DCM (160 mL) were addedimidazole (1.05 eq.), TBDMSCl (1.05 eq.) and DMAP (0.1 eq.). The mixturewas stirred at rt for 1 h. Water was added and the mixture was extractedwith DCM. The org. layer was dried over MgSO₄ and concentrated to affordthe title intermediate as a yellow oil (4.52 g, 77%).

MS (ESI, m/z): 353.2 [M+H⁺].

AX.iv.[(S)-2-(tert-butyl-dimethyl-silanyloxy)-1-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]-carbamicacid tert-butyl ester

Starting from intermediate AX.iii (4.52 g) and using procedure N′, thetitle intermediate was obtained as a light yellow oil (6.76 g, quant.).

MS (ESI, m/z): 452.2 [M+H⁺].

AX.v.[(S)-1-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-2-hydroxy-ethyl]-carbamicacid tert-butyl ester

Starting from intermediate AX.iv (6.76 g) and using procedure J, thetitle intermediate was obtained as a yellow oil (3.96 g, 78% yield).

MS (ESI, m/z): 338.2 [M+H⁺].

AX.vi.((S)-3-fluoro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de][1,5]naphthyridin-4-yl)-carbamicacid tert-butyl ester

Starting from intermediate AX.v (3.46 g) and using procedure H followedby heating at 80° C. for 18 h in DCE, the title intermediate wasobtained as a yellow oil (0.90 g, 28% yield).

MS (ESI, m/z): 306.2 [M+H⁺].

AX.vii.rac-4-amino-3-fluoro-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from intermediate AX.vi (0.875 g) and using procedure B, thetitle intermediate was obtained as a pale yellow solid (0.42 g, 71%yield). An analysis of the ee-value indicated that the product waspresent as a racemate. Since no ee-determinations in previous steps havebeen made, a racemisation at an earlier stage in the synthetic sequencecannot be excluded.

MS (ESI, m/z): 206.1 [M+H⁺].

Preparation AY: methanesulfonic acid2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylester

Starting from tert-butyl-dimethyl-[(S)-2-oxiranyl-ethoxy]-silane, thetitle compound was prepared in analogy to Preparation I.

The analytical data were identical with those of the compound ofPreparation I.

Preparation AZ:(R)-6-amino-7-fluoro-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

The title compound was prepared as described in Preparation AD, usinghowever AD-mix α in the first step.

The analytical data were identical with those of the compound ofPreparation AD.

Preparation BA:6-{5-[(1RS)-1-(tert-butyl-dimethyl-silanyloxy)-3-hydroxy-propyl]-((5RS)-2-oxo-oxazolidin-3-yl)}-4H-benzo[1,4]thiazin-3-oneBA.i.(3RS)-3-(tert-butyl-dimethyl-silanyloxy)-3-((2RS)-oxiran-2-yl)-propionicacid tert-butyl ester

A solution of 3-[[(tert-butyl-dimethylsilyl]oxy]-4-pentenoic acidtert-butyl ester (3.60 g; prepared according to J. Org. Chem. (1994),59, 4760-4764) in DCM (100 mL) was reacted with MCPBA (3.96 g) for 2days. The reaction mixture was partitioned between DCM and an aq.solution containing Na₂S₂O₃ (10%) and NaHCO₃ (sat.). The org. phase wasseparated, dried over MgSO₄, evaporated under reduced pressure andpurified by CC (Hept/EA 9:1 to 4:1), affording a colourless liquid (2.55g; 67% yield; 3:2 mixture of diastereomers).

¹H NMR (CDCl₃) δ: 4.02 (m, 1H, diast. B), 3.76 (d, J=6.4 Hz, 1H, diast.A), 3.02 (m, 1H, diast. A), 2.99 (m, 1H, diast. B), 2.8-2.4 (m, 4H,diast. A and B), 1.45 (s, 9H, diast. A and B), 0.88 (m, 9H, diast. A andB), 0.10 (m, 6H, diast. A and B).

BA.ii.(3RS)-3-(tert-butyl-dimethyl-silanyloxy)-(4RS)-4-hydroxy-5-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-ylamino)-pentanoicacid tert-butyl ester

A solution of intermediate BA.i (6.05 g) and6-amino-4H-benzo[1,4]thiazin-3-one (3.60 g) in EtOH/water (9:1; 100 mL)was refluxed for 30 h. The org. solvent was removed under reducedpressure and the residue was taken up in EA (20 mL) and filtered. Thefiltrate was concentrated under reduced pressure and purified by CC(Hept/EA 1:1 to 1:2), affording after trituration in EA/ether, acolourless solid (3.26 g; 34% yield).

MS (ESI, m/z): 483.2 [M+H⁺].

BA.iii.(3RS)-3-(tert-butyl-dimethyl-silanyloxy)-3-[((5RS)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl))-oxazolidin-5-yl]-propionicacid tert-butyl ester

Starting from intermediate BA.ii (3.25 g) and following procedure I, thetitle compound was obtained as a colourless solid (3.27 g; 95% yield).

MS (ESI, m/z): 509.1 [M+H⁺].

BA.iv.6-{-[(1RS)-1-(tert-butyl-dimethyl-silanyloxy)-3-hydroxy-propyl]-((5RS)-2-oxo-oxazolidin-3-yl)}-4H-benzo[1,4]thiazin-3-one

Starting from intermediate BA.iii (1.01 g) and following procedure A,the title compound was obtained, after CC (Hept/EA 2:1 then 0:1), as acolourless foam (205 mg; 23% yield).

MS (ESI, m/z): 439.1 [M+H⁺].

Preparation BB:(R)-6-amino-7-fluoro-2-methoxy-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-oneBB.i. 6-fluoro-2,3-dimethoxy-quinoxaline-5-carbaldehyde

A solution of tetramethylpiperidine (16.4 mL) in dry THF (100 mL) wascooled to −78° C. and treated dropwise with n-BuLi (2.5M in Hex; 39 mL).The solution was further stirred at −78° C. for 30 min. A solution of6-fluoro-2,3-dimethoxy-quinoxaline (15.6 g; prepared from thecommercially available 2,3-dichloro-6-fluoroquinoxaline according toEgyptian Journal of Chemistry (1980), Volume Date 1977, 20, 427-39) indry THF (450 mL) was cooled to −78° C., treated dropwise with the firstsolution and further stirred at −78° C. for 30 min. The resultingreaction mixture was treated with DMF (11.56 mL) and further stirred at−78° C. for 15 min. The reaction mixture was poured onto a mixture of asat. NH₄Cl solution and ice and extracted with ether. The org. layer waswashed with brine, dried over MgSO₄, evaporated under reduced pressureand crystallised from Hex/EA affording a light yellow solid (12.5 g; 71%yield).

¹H NMR (CDCl₃) δ: 11.10 (d, J=0.6 Hz, 1H), 7.96 (dd, J=9.1, 5.3 Hz, 1H),7.30 (m, 1H), 4.19 (m, 3H), 4.15 (m, 3H).

BB.ii. 6-fluoro-2,3-dimethoxy-5-vinyl-quinoxaline

A suspension of methyltriphenylphosphonium bromide (18.15 g) in THF (200mL) was treated with tBuOK (5.7 g). After stirring for 1 h, the solutionwas cooled to 0° C. and treated with a solution of intermediate BB.i(10.0 g) in THF (100 mL). The reaction mixture was further stirred at rtfor 3 h and sequentially washed with water and with a sat. NH₄Clsolution. The org. layer was dried over MgSO₄, evaporated and purifiedby CC (Hex/EA 4:1 to 2:1), affording a colourless solid (8.80 g; 89%yield).

¹H NMR (CDCl₃) δ: 7.62 (dd, J=8.8, 5.3 Hz, 1H), 7.46 (m, 1H), 7.25 (m,1H), 6.34 (m, 1H), 5.69 (m, 1H), 4.17 (s, 3H), 4.13 (s, 3H).

BB.iii. (S)-1-(6-fluoro-2,3-dimethoxy-quinoxalin-5-yl)-ethane-1,2-diol

Starting from intermediate BB.ii (8.70 g) and using procedure L withAD-mix α, the title compound was obtained as a beige solid (5.60 g; 56%yield) after crystallization from ether.

¹H NMR (DMSO d6) δ: 7.67 (dd, J=9.1, 5.6 Hz, 1H), 7.35 (dd, J=10.3, 9.1Hz, 1H), 5.56 (m, 1H), 5.20 (d, J=6.4 Hz, 1H), 4.73 (t, J=6.2 Hz, 1H),4.05 (s, 3H), 4.01 (s, 3H), 3.87 (m, 1H), 3.69 (m, 1H).

BB.iv.(S)-2-(tert-butyl-dimethyl-silanyloxy)-1-(6-fluoro-2,3-dimethoxy-quinoxalin-5-yl)-ethanol

Starting from intermediate BB.iii (5.50 g) and using procedure M, thetitle compound was obtained, after purification by CC (Hept/EA 2:1), asa yellow oil (7.40 g; 94% yield).

MS (ESI, m/z): 383.2 [M+H⁺].

BB.v.[(R)-2-(tert-butyl-dimethyl-silanyloxy)-1-(6-fluoro-2,3-dimethoxy-quinoxalin-5-yl)-ethyl]-carbamicacid tert-butyl ester

Starting from intermediate BB.iv (7.30 g) and using procedure N′, thetitle compound was obtained, after purification by CC (Hept/EA 9:1 t4:1), as a yellow oil (6.7 g, 73% yield).

¹H NMR (CDCl₃) δ: 7.66 (dd, J=9.1, 5.6 Hz, 1H), 7.23 (m, 1H), 6.50 (m,1H), 4.17 (s, 3H), 4.13 (s, 3H), 3.92 (d, J=6.4 Hz, 2H), 1.42 (s, 9H),0.76 (s, 9H), −0.09 (s, 3H), −0.14 (s, 3H).

BB.vi.[(R)-1-(6-fluoro-2,3-dimethoxy-quinoxalin-5-yl)-2-hydroxy-ethyl]-carbamicacid tert-butyl ester

Starting from intermediate BB.v (6.70 g) and using procedure J, thetitle compound was obtained, after crystallization from Hept/EA 1:1, asa colourless solid (3.60 g; 70% yield).

¹H NMR (CDCl₃) δ: 7.69 (dd, J=9.1, 5.6 Hz, 1H) 7.26 (m, 1H), 6.60 (m,1H), 5.80 (m, 1H), 4.17 (s, 3H), 4.13 (s, 3H), 3.95 (m, 2H), 1.43 (s,9H).

BB.vii.((R)-7-fluoro-2-methoxy-3-oxo-5,6-dihydro-3H-pyrrolo[1,2,3-de]quinoxalin-6-yl)-carbamicacid tert-butyl ester

Starting from intermediate BB.vi (3.50 g) and using procedure H, theintermediate mesylate was formed. The reaction mixture was furtherstirred at reflux for 12 h, cooled to rt, washed with water. The org.layer was dried over MgSO₄ and concentrated under reduced pressureaffording a crude solid (2.70 g, 84% yield) containing the titlecompound in a 3:2 mixture with(R)-4-(6-fluoro-2,3-dimethoxy-quinoxalin-5-yl)-oxazolidin-2-one. Themixture was used without any further purification in the next step.

BB.viii.(R)-6-amino-7-fluoro-2-methoxy-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from intermediate BB.vii (2.70 g) and using procedure B, thetitle compound was obtained after purification by CC (EA/MeOH 9:1containing 1% NH₄OH) as a colourless solid (469 mg; 25% yield).

MS (ESI, m/z): 236.2 [M+H⁺].

Preparation BC: (R)-1-amino-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

The title compound was prepared in analogy to Preparation AS, usinghowever AD-mix α in the second step.

The analytical data were identical with those of the compound ofPreparation AS.

Preparation BD: toluene-4-sulfonic acid(R)-4-hydroxy-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de][1,5]naphthyridin-4-ylmethylester BD.i. 2-(6-methoxy-[1,5]naphthyridin-4-yl)-propane-1,3-diol

A solution of 2-methoxy-8-methyl-1,5-naphthyridine (2.90 g; preparedaccording to WO 00/21948) in aq. formaldehyde (37%; 7.8 mL) was heatedat 100° C. for 3 days. After cooling to rt, the reaction mixture wasconcentrated to dryness and the residue was taken up in MeOH (10 mL) andconcentrated again. The residue was purified by CC (DCM/MeOH/NH₄OH1000:100:8) to give a colourless solid (2.78 g; 71% yield).

¹H NMR (DMSO-d₆) δ: 8.67 (d, J=4.4 Hz, 1H), 8.22 (d, J=9.1 Hz, 1H), 7.51(d, J=4.4 Hz, 1H), 7.22 (d, J=9.1 Hz, 1H), 4.56 (m, 2H), 4.00 (m, 4H),3.84 (m, 4H).

BD.ii. Acetic acid(S)-3-hydroxy-2-(6-methoxy-[1,5]naphthyridin-4-yl)-propyl ester

A solution of intermediate BD.i (1.34 g) in vinyl acetate (10 mL) wastreated with powdered 3 Å molecular sieves (78 mg) and stirred at rt for15 min under an atmosphere of nitrogen. Lipase acrylic resin fromCandida antarctica (600 mg, Sigma L4777) was added and stirring wascontinued for 4 h at rt. The polymer bound enzyme was filtered off, thefilter cake was rinsed with THF and the filtrate was concentrated. Theresidue was purified by CC (DCM/MeOH/NH₄OH 1000:25:2), affording acolourless oil (0.688 g; 44% yield).

¹H NMR (CDCl₃) δ: 8.72 (d, J=4.7 Hz, 1H), 8.23 (d, J=9.1 Hz, 1H), 7.46(d, J=4.7 Hz, 1H), 7.15 (d, J=9.1 Hz, 1H), 4.64 (m, 2H), 4.24 (m, 1H),4.08 (m, 5H), 2.05 (s, 3H).

BD.iii. Acetic acid(S)-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de][1,5]naphthyridin-4-ylmethylester

A solution of intermediate BD.ii (2.05 g) in DCM (40 mL) was transformedinto the corresponding mesylate using procedure H. After fullconsumption of the alcohol, DCE (40 mL) was added and the solution wasfurther stirred at 60° C. for 4 h. After cooling to rt, water was addedand the two layers were decanted and the aq. layer was extracted oncemore with DCM. The combined org. layers were concentrated to dryness.The residue was triturated with TBME, affording a grey solid (1.40 g;77% yield).

¹H NMR (CDCl₃) δ: 8.53 (d, J=4.7 Hz, 1H), 7.93 (d, J=9.7 Hz, 1H), 7.34(dd, J=4.7, 0.9 Hz, 1H), 6.90 (d, J=9.7 Hz, 1H), 4.57 (dd, J=12.9, 9.4Hz, 1H), 4.37 (d, J=6.4 Hz, 2H), 4.27 (dd, J=13.2, 5.0 Hz, 1H), 4.09 (m,1H), 2.06 (s, 3H).

BD.iv.(S)-4-hydroxymethyl-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

To a solution of intermediate BD.iii (1.11 g) in MeOH (30 mL), cooled to−10° C., K₂CO₃ (313 mg, 0.5 eq.) was added and the mixture wasvigorously stirred at 0° C. for 20 min. The mixture was concentrated andthe residue was purified by CC (DCM/MeOH/NH₄OH 1000:100:8), affording acolourless solid (773 mg; 84% yield).

MS (ESI, m/z): 203.0 [M+H⁺].

BD.v. Methanesulfonic acid(S)-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de][1,5]naphthyridin-4-ylmethylester

A solution of intermediate BD.iv (600 mg) in DCM (30 mL) was transformedinto the corresponding mesylate using procedure H. The crude material(1.03 g) was used in the next step without any further purification.

MS (ESI, m/z): 281.2 [M+H⁺].

BD.vi. 4-methylene-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

A solution of intermediate BD.v (1.03 g) in DMF (10 mL) was stirred atrt in the presence of DBU (1.12 mL) for 2 h. The reaction mixture wasdiluted with EA and water. The aq. layer was extracted with EA (2×100mL) and DCM/MeOH (3×50 mL; 9:1). The combined org. layers weresequentially washed with water and brine and dried over MgSO₄. Thesolvent was evaporated under reduced pressure, affording a yellow solid(490 mg; 72% yield).

¹H NMR (CDCl₃) δ: 8.55 (d, J=5.0 Hz, 1H), 7.96 (d, J=9.7 Hz, 1H), 7.44(d, J=5.0 Hz, 1H), 6.92 (d, J=9.7 Hz, 1H), 6.00 (td, J=2.9, 0.9 Hz, 1H),5.65 (td, J=2.6, 0.9 Hz, 1H), 5.02 (t, J=2.6 Hz, 2H).

BD.vii.(R)-4-hydroxy-4-hydroxymethyl-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

A solution of intermediate BD.vi (240 mg) was dihydroxylated in presenceof AD-mix α using procedure L. The crude yellow solid (216 mg; 76%yield) was used in the next step without any further purification.

¹H NMR (CDCl₃) δ: 8.55 (d, J=4.7 Hz, 1H), 7.90 (m, 1H), 7.53 (d, J=4.7Hz, 1H), 6.81 (m, 1H), 4.35 (m, 2H), 3.89 (m, 3H).

BD.viii. Toluene-4-sulfonic acid(R)-4-hydroxy-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de][1,5]naphthyridin-4-ylmethylester

A solution of intermediate BD.vii (210 mg) was stirred at rt overnightin presence of TEA (0.20 mL), TsCl (185 mg) and dibutyltin oxide (12mg). The reaction mixture was diluted with water (3 mL). The org. layerwas washed with sat. NaHCO₃ and brine and dried over MgSO₄. The solventwas evaporated under reduced pressure, affording an off-white solid (172mg; 48% yield).

MS (ESI, m/z): 373.0 [M+H⁺].

Preparation BE:rac-1-amino-9-bromo-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one BE.i.(7-bromo-2-methoxy-quinolin-8-yl)-methanol

A suspension of 7-bromo-8-bromomethyl-2-(methyloxy)quinoline (35.2 g;prepared according to WO 2007/081597; containing 20% of debrominatedcompound) in acetone/water (1:1; 860 mL) was refluxed for 6 h inpresence of NaHCO₃ (14.63 g). The org. solvent was removed under reducedpressure and the residue was extracted with EA. The org. layer waswashed with brine and dried over Na₂SO₄. The solvent was then evaporatedand the residue was crystallized from TBDME, affording an off-whitesolid (16.0 g; 56% yield).

MS (ESI, m/z): 268.0 [M+H⁺].

BE.ii. 7-bromo-2-methoxy-quinoline-8-carbaldehyde

A solution of oxalyl chloride (9.47 mL) in DCM (200 mL) was cooled to−78° C. and treated dropwise with a solution of DMSO (9.52 mL) in DCM(80 mL). After stirring for 15 min, the solution was treated with asolution of intermediate BE.i (10.0 g) in DCM (80 mL). After furtherstirring at −78° C. for 3 h, the reaction mixture was treated dropwisewith a solution of TEA (39.0 mL) in DCM (80 mL) over 1 h. The reactionmixture was further stirred for 40 min and allowed to reach rt. Thereaction mixture was than treated with a sat. NaHCO₃ solution. The org.layer was separated and washed with brine, dried over Na₂SO₄. Thesolvent was evaporated and the residue was dissolved in EA and filteredthrough a pad of silica gel, affording a pale yellow solid (3.74 g; 38%yield).

¹H NMR (DMSO-d₆) δ: 11.06 (s, 1H), 8.36 (d, J=8.8 Hz, 1H), 8.04 (d,J=8.8 Hz, 1H), 7.74 (m, 1H), 7.17 (d, J=8.8 Hz, 1H), 4.01 (s, 4H).

BE.iii. 7-bromo-2-methoxy-8-vinyl-quinoline

To a solution of methyltriphenylphosphonium bromide (1.00 g) in THF (8mL) cooled to −78° C. was added n-BuLi (2.5M in Hex, 1.09 mL, 1.5 eq.).The mixture was stirred 15 min at this temperature and then 45 min at 0°C. before cooling again to −78° C. A solution of intermediate BE.ii (500mg) in THF (8 mL) was quickly added. The reaction proceeded overnightwith gradual warming to rt. MeOH was added to quench the reaction andthe mixture was concentrated under reduced pressure. The residue waspurified by CC (Hept/EA 4:1 to 2:1), affording the title compound as ayellowish oil (411 mg; 83% yield).

MS (ESI, m/z): 264.3 [M+H⁺].

BE.iv. rac-1-(7-bromo-2-methoxy-quinolin-8-yl)-ethane-1,2-diol

Starting from intermediate BE.iii (5.50 g) and proceeding in analogy toPreparation AX, step AX.ii, using however K₂OsO₄/NMO instead of AD-mix βand omitting the use of methylsulfonamide, the title compound wasobtained as a beige solid (5.75 g, 93% yield) after crystallization fromTBDME.

¹H NMR (CDCl₃) δ: 8.01 (d, J=9.1 Hz, 1H), 7.58 (m, 1H), 7.50 (m, 1H),6.97 (m, 1H), 5.53 (m, 1H), 4.07 (s, 3H), 3.91 (m, 2H).

BE.v.rac-1-(7-bromo-2-methoxy-quinolin-8-yl)-2-(tert-butyl-dimethyl-silanyloxy)-ethanol

Starting from intermediate BE.iv (5.70 g) and using procedure M, thetitle compound was obtained as a brown oil (7.79 g, 99% yield).

¹H NMR (CDCl₃) δ: 7.97 (d, J=8.8 Hz, 1H), 7.55 (m, 1H), 7.45 (m, 1H),6.93 (d, J=8.8 Hz, 1H), 5.54 (t, J=5.6 Hz, 1H), 4.12 (m, 1H), 4.04 (s,3H), 3.98 (m, 1H), 0.75 (m, 9H), −0.14 (d, J=0.9 Hz, 6H).

BE.vi.rac-1-(7-bromo-2-methoxy-quinolin-8-yl)-2-(tert-butyl-dimethyl-silanyloxy)-ethylamine

Starting from intermediate BE.v (7.75 g), the title compound wasprepared in analogy to Preparation Z, step Z.iv. A yellow oil (2.6 g;33% yield) was obtained.

MS (ESI, m/z): 411.3 [M+H⁺].

BE.vii.rac-[1-(7-bromo-2-methoxy-quinolin-8-yl)-2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-carbamicacid tert-butyl ester

Starting from intermediate BE.vi (2.60 g) and using procedure G, thetitle compound was obtained as a yellow oil (3.20 g, 99% yield).

¹H NMR (CDCl₃) δ: 7.95 (d, J=9.1 Hz, 1H), 7.55 (m, 1H), 7.44 (m, 1H),6.92 (d, J=9.1 Hz, 1H), 6.35 (m, 1H), 4.97 (m, 1H), 4.06 (m, 3H), 4.03(m, 1H), 3.74 (m, 1H), 1.25 (m, 9H), 0.75 (s, 9H), −0.11 (s, 6H).

BE.viii.rac-[1-(7-bromo-2-methoxy-quinolin-8-yl)-2-hydroxy-ethyl]-carbamic acidtert-butyl ester

Starting from intermediate BE.vii (3.20 g) and using procedure J, thetitle compound was obtained as an off-white solid (1.70 g, 68% yield).

¹H NMR (CDCl₃) δ: 7.98 (d, J=9.1 Hz, 1H), 7.60 (m, 1H), 7.49 (m, 1H),6.96 (d, J=8.8 Hz, 1H), 5.92 (m, 1H), 4.08 (m, 4H), 4.03 (m, 2H), 1.44(s, 9H).

BE.ix.rac-(9-bromo-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamicacid tert-butyl ester

Starting from intermediate BE.viii (400 mg) and using the same procedureas for the preparation of intermediate Z.vi, the title compound wasobtained as a yellow solid (372 mg, 100% yield).

¹H NMR (CDCl₃) δ: 7.67 (d, J=9.4 Hz, 1H), 7.32 (m, 2H), 6.68 (m, 1H),5.58 (m, 1H), 4.97 (m, 1H), 4.64 (m, 1H), 4.32 (m, 1H), 1.24 (m, 9H).

MS (ESI, m/z): 365.3 [M+H⁺].

BE.x. rac-1-amino-9-bromo-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from intermediate BE.ix (100 mg) and using procedure B, thetitle compound was obtained as an off-white solid (52 mg, 72% yield).

¹H NMR (CDCl₃) δ: 7.67 (d, J=9.7 Hz, 1H), 7.33 (m, 2H), 6.68 (d, J=9.7Hz, 1H), 4.89 (dd, J=8.8, 3.5 Hz, 1H), 4.62 (dd, J=13.5, 8.5 Hz, 1H),4.17 (dd, J=13.5, 3.8 Hz, 1H), 1.80 (m, 2H).

Preparation BF:(R)-1-amino-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-7-carboxylicacid ethyl ester

BF.i. 2-methoxy-8-vinyl-quinoline-5-carboxylic acid ethyl ester

A solution of vinylboronic anhydride pyridine complex (1:1; 3.81 g) inDMF (240 mL) was treated with tetrakis(triphenylphosphine)palladium(0)(731 mg) and stirred under nitrogen for 20 min. The reaction mixture wassequentially treated with K₂CO₃ (4.372 g) water (73 mL) and2-methoxy-8-[[(trifluoromethyl)sulfonyl]oxy]-5-quinoline carboxylic acidethyl ester (12.0 g; prepared in analogy to the corresponding n-butylester described in WO 2006/046552) and further stirred at 85° C.overnight. The reaction mixture was diluted with water and extractedwith ether. The org. layer was dried over MgSO₄, concentrated to drynessand purified by CC (Hex/EA, 4:1), affording a yellow oil (5.40 g; 66%yield).

¹H NMR (CDCl₃) δ: 9.20 (d, J=9.1 Hz, 1H), 8.08 (dd, J=7.9, 0.6 Hz, 1H),7.96 (dd, J=18.2, 11.1 Hz, 1H), 7.86 (d, J=7.9 Hz, 1H), 7.02 (d, J=9.4Hz, 1H), 6.05 (dd, J=18.2, 1.5 Hz, 1H), 5.54 (dd, J=11.1, 1.5 Hz, 1H),4.45 (q, J=7.3 Hz, 2H), 4.10 (s, 3H), 1.45 (t, J=7.0 Hz, 3H).

BF.ii. 8-((S)-1,2-dihydroxy-ethyl)-2-methoxy-quinoline-5-carboxylic acidethyl ester

A solution of intermediate BF.i (5.40 g) was dihydroxylated in thepresence of AD-mix α using procedure L. After crystallization fromether, the product was obtained as a white solid (4.30 g; 70% yield;enantiomeric excess not checked, assumed 100%).

¹H NMR (DMSO d6) δ: 9.05 (d, J=9.4 Hz, 1H), 8.04 (m, 1H), 7.87 (d, J=7.9Hz, 1H), 7.15 (d, J=9.4 Hz, 1H), 5.66 (m, 1H), 5.35 (m, 1H), 4.67 (m,1H), 4.37 (q, J=7.0 Hz, 2H), 4.00 (s, 3H), 3.79 (m, 1H), 3.43 (m, 1H),1.35 (t, J=7.3 Hz, 3H)

BF.iii.8-[(S)-2-(tert-butyl-dimethyl-silanyloxy)-1-hydroxy-ethyl]-2-methoxy-quinoline-5-carboxylicacid ethyl ester

Starting from intermediate BF.ii (4.20 g) and using procedure M, thetitle intermediate was obtained as a yellow oil (5.48 g; 94% yield).

MS (ESI, m/z): 406.2 [M+H⁺].

BF.iv.8-[(R)-1-tert-butoxycarbonylamino-2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-methoxy-quinoline-5-carboxylicacid ethyl ester

A solution of intermediate BF.iii (5.30 g) and PPh₃ (4.11 g) in THF (130mL) was cooled to 0° C. and treated dropwise with DPPA (3.4 mL) and DIAD(3.36 mL). The reaction mixture was stirred at 0° C. for 15 min than atrt for 1.5 h. The reaction mixture was evaporated to dryness andpurified by CC (Hept/EA 2:1), affording the intermediate azide as ayellow oil (6.0 g). The latter was dissolved in THF/water (9:1; 50 mL),treated with PPh₃ (4.1 g) and stirred at 50° C. for 1.5 h. The reactionmixture was then reacted with Boc₂O (5.7 g) and further stirred at rtover the weekend. The reaction mixture was concentrated under reducedpressure and purified by CC (Hept/EA 9:1 to 4:1), affording a yellow oil(9.20 g; contaminated by remaining Boc₂O).

¹H NMR (CDCl₃) δ: 9.21 (d, J=9.4 Hz, 1H), 8.05 (d, J=7.9 Hz, 1H), 7.59(d, J=7.6 Hz, 1H), 7.01 (d, J=9.4 Hz, 1H), 5.64 (t, J=4.7 Hz, 1H), 4.44(q, J=7.0 Hz, 2H), 4.07 (m, 5H), 1.50 (m, 3H), 1.44 (s, 9H), 0.76 (s,9H), −0.23 (m, 6H).

BF.v.8-((R)-1-tert-butoxycarbonylamino-2-hydroxy-ethyl)-2-methoxy-quinoline-5-carboxylicacid ethyl ester

Starting from intermediate BF.iv (6.56 g) and using procedure J, thetitle intermediate was obtained as a colourless solid (2.60 g; 51%yield).

¹H NMR (CDCl₃) δ: 9.22 (d, J=9.4 Hz, 1H), 8.06 (d, J=7.6 Hz, 1H), 7.62(d, J=7.9 Hz, 1H), 7.04 (d, J=9.4 Hz, 1H), 5.55 (m, 1H), 4.44 (q, J=7.3Hz, 2H), 4.03 (m, 5H), 1.44 (s, 9H).

BF.vi.(R)-1-tert-butoxycarbonylamino-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-7-carboxylicacid ethyl ester

Starting from intermediate BF.v (2.40 g) and using procedure H, thetitle intermediate was obtained as a colourless solid after triturationin ether (2.10 g; 95% yield).

MS (ESI, m/z): 359.2 [M+H⁺].

BF.vii.(R)-1-amino-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-7-carboxylicacid ethyl ester

Starting from intermediate BF.vi (1.00 g) and using procedure B, thetitle compound was obtained as a beige solid (690 mg; 96% yield).

MS (ESI, m/z): 259.2 [M+H⁺].

Preparation BG:(R)-1-amino-7-hydroxymethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-oneBG.i.((R)-7-hydroxymethyl-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamicacid tert-butyl ester

Starting from intermediate BF.vi (250 mg) and using procedure A, thetitle intermediate was obtained as a yellowish solid after triturationin ether (190 mg; 86% yield).

MS (ESI, m/z): 317.2 [M+H⁺].

BG.ii.(R)-1-amino-7-hydroxymethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from intermediate BG.i (180 mg) and using procedure B, thetitle compound was isolated from the water phase after evaporation todryness and suspension in DCM/MeOH (9:1), affording 400 mg of a beigesolid (contaminated by inorganic salts). The material was used withoutany further purification in the next steps.

¹H NMR (DMSO d6) δ: 8.10 (d, J=9.7 Hz, 1H), 7.65 (d, J=7.6 Hz, 1H), 7.27(d, J=7.6 Hz, 1H), 6.61 (d, J=9.7 Hz, 1H), 5.41 (m, 1H), 5.19 (m, 1H),4.79 (m, 2H), 4.55 (dd, J=13.5, 8.5 Hz, 1H), 4.22 (dd, J=13.5, 3.2 Hz,1H), 4.07 (ddd, J=3.2, 2.1, 0.9 Hz, 1H).

Preparation BH:(R)-1-amino-7-dimethylaminomethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-oneBH.i.((R)-7-formyl-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamicacid tert-butyl ester

A solution of intermediate BG.i (640 mg) in DCM/THF (40 mL; 2:1) wasstirred in the presence of MnO₂ (3.75 g) for 30 min. The reactionmixture was filtered through Celite® and the filtrate was evaporated todryness. The residue was triturated in ether/Hept, affording a yellowsolid (480 mg; 75% yield).

¹H NMR (CDCl₃) δ: 10.19 (s, 1H), 8.84 (d, J=9.7 Hz, 1H), 7.69 (m, 2H),6.81 (d, J=9.7 Hz, 1H), 5.66 (m, 1H), 5.11 (m, 1H), 4.74 (dd, J=13.8,9.1 Hz, 1H), 4.25 (m, 1H), 1.45 (m, 9H).

BH.ii.((R)-7-dimethylaminomethyl-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamicacid tert-butyl ester

Starting from intermediate BH.i (200 mg) and NHMe₂ (0.11 mL; 5.6M inEtOH) and using procedure E, the title intermediate was obtained as ayellow solid (140 mg; 64% yield).

MS (ESI, m/z): 344.6 [M+H⁺].

BH.iii.(R)-1-amino-7-dimethylaminomethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from intermediate BH.ii (140 mg) and using procedure B, thetitle compound was obtained as an orange oil (74 mg; 76% yield).

MS (ESI, m/z): 244.3 [M+H⁺].

Preparation BI:(R)-1-amino-7-pyrrolidin-1-ylmethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-oneBI.i.((R)-4-oxo-7-pyrrolidin-1-ylmethyl-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamicacid tert-butyl ester

Starting from intermediate BH.i (200 mg) and pyrrolidine (52 μL) andusing procedure E, the title intermediate was obtained as a yellow solid(190 mg; 80% yield).

MS (ESI, m/z): 370.4 [M+H⁺].

BI.ii.(R)-1-amino-7-pyrrolidin-1-ylmethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from intermediate BI.i (190 mg) and using procedure B, thetitle compound was obtained as an orange oil (100 mg; 72% yield).

MS (ESI, m/z): 269.9 [M+H⁺].

Preparation BJ:3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propionaldehyde

The title compound was prepared in analogy to Preparation AR, startinghowever from (S)-2-[2-[[(tert-butyl)dimethylsilyl]oxy]propyl]-oxirane.The yields were similar and the analytical data (MS, ¹H NMR) wereidentical.

Preparation BK:3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propionaldehydeBK.i. (2-tert-butoxycarbonylamino-6-chloro-pyridin-3-ylsulfanyl)-aceticacid ethyl ester

A solution of TMEDA (1.677 mL) in THF (20 mL) was cooled to −20° C. andtreated dropwise with 2.3M n-BuLi (4.75 mL). After stirring at thistemperature for 20 min, the solution was cooled to −78° C. and treateddropwise with a solution of 2-tert-butoxycarbonylamino-6-chloropyridine(1.14 g; commercial) in THF (7.5 mL). The solution was further stirredat this temperature for 1 h and treated with sulfur (S8). After furtherstirring at this temperature for 20 min the reaction mixture was treatedwith ethyl bromoacetate (0.86 mL). After further stirring for 2 h at−78° C., the temperature was allowed to reach −45° C. and quenched bythe addition of EA and water. The org phase was sequentially washed with1N HCl, conc. NH₄Cl solution and brine. The org. phase was dried overMgSO₄ and the solvents were evaporated. The residue was purified by CC(Hept/EA 4:1 to 2:1), affording a colourless oil (1.05 g; 60% yield).

¹H NMR (CDCl₃) δ: 8.01 (s, 1H), 7.79 (d, J=8.2 Hz, 1H), 6.98 (d, J=8.2Hz, 1H), 4.14 (q, J=7.0 Hz, 3H), 3.47 (s, 2H), 1.54 (s, 12H), 1.22 (t,J=7.0 Hz, 3H).

BK.ii. 6-chloro-4H-pyrido[3, 2-b][1,4]thiazin-3-one

A solution of intermediate BK.i (1.0 g) in DCM (6 mL) was stirred at rtovernight in the presence of TFA (6 mL). The reaction mixture wasevaporated to dryness and the residue was dissolved in EtOH and refluxedfor 2 days. The reaction mixture was evaporated to dryness and theresidue was taken up in EA and a sat. aq. NaHCO₃ solution. The org.layer was washed with brine, dried over MgSO₄, concentrated underreduced pressure and crystallized from ether/Hept, affording a yellowsolid (400 mg; 69% yield).

¹H NMR (CDCl₃) δ: 8.28 (d, J=1.5 Hz, 1H), 7.57 (dd, J=8.2, 0.6 Hz, 1H),6.98 (d, J=8.2 Hz, 1H), 3.50 (m, 2H).

BK.iii.6-{(R)-5-[3-(tert-butyl-dimethyl-silanyloxy)-propyl]-2-oxo-oxazolidin-3-yl}-4H-pyrido[3,2-b][1,4]thiazin-3-one

A vial was charged with intermediate BK.ii (2 g), palladium(II)acetate(224 mg), DPEphos (1.08 g), potassium phosphate tribasic (powdered; 4.33g) and intermediate AR.ii (3.1 g). Dioxane (dry, over molecular sieves,50 mL) was then added using a syringe and the resulting suspension wassparged with argon for 5 min. The mixture was then heated in a sealedflask at 80° C. overnight. The residue was extracted with EA/water. Theorg. layer was washed with brine, dried over MgSO₄ and concentrated. Theresidue was purified by CC (Hept/EA 2:1, 1:1) affording a yellowishsolid (3.58 g; 84% yield).

¹H NMR (DMSO d6) δ: 10.81 (s, 1H), 7.77 (m, 1H), 7.66 (m, 1H), 4.71 (m,1H), 4.20 (m, 1H), 3.69 (dd, J=10.5, 7.3 Hz, 1H), 3.62 (t, J=6.4 Hz,2H), 3.51 (s, 2H), 1.74 (m, 2H), 1.56 (dd, J=9.4, 7.3 Hz, 2H), 0.85 (m,9H), 0.02 (s, 6H).

BK.iv.6-[(R)-5-(3-hydroxy-propyl)-2-oxo-oxazolidin-3-yl]-4H-pyrido[3,2-b][1,4]thiazin-3-one

Starting from intermediate BK.iii (3.58 g) and using procedure J, thetitle intermediate was obtained as a colourless solid (2.0 g; 76%yield).

¹H NMR (DMSO d6) δ: 10.83 (s, 1H), 7.77 (m, 1H), 7.66 (m, 1H), 4.70 (m,1H), 4.48 (t, J=5.3 Hz, 1H), 4.20 (m, 1H), 3.70 (dd, J=10.3, 7.0 Hz,1H), 3.51 (s, 2H), 3.43 (q, J=6.2 Hz, 2H), 3.28 (s, 3H), 1.75 (m, 2H),1.51 (m, 2H).

BK.v.3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl-oxazolidin-5-yl]-propionaldehyde

Starting from intermediate BK.iv (250 mg) and using the procedure ofPreparation U, step U.iv, the title compound was obtained as acolourless solid (200 mg; 80% yield).

MS (ESI, m/z): 308.3 [M+H⁺].

Preparation BL:3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propionaldehyde

The title compound was prepared in analogy to Preparation BK, startinghowever from (S)-2-[2-[[(tert-butyl)dimethylsilyl]oxy]propyl]-oxirane.The yields were similar and the analytical data (MS, ¹H NMR) wereidentical.

Preparation BM:(R)-4-amino-3-fluoro-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-oneBM.i. rac-1-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-ethane-1,2-diol

Starting from intermediate Ax.i (12.75 g) and proceeding in analogy toPreparation AX, step AX.ii, using however K₂OsO₄/NMO instead of AD-mix βand omitting the use of methylsulfonamide, the title compound wasisolated as a light brown solid (9.80 g; 66% yield).

MS (ESI, m/z): 238.4 [M+H⁺].

BM.ii.rac-2-(tert-butyl-dimethyl-silanyloxy)-1-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-ethanol

Starting from intermediate BM.i (12.35 g) and using procedure M, thetitle intermediate was obtained as a brown oil (18.85 g; 100% yield).

MS (ESI, m/z): 353.4 [M+H⁺].

BM.iii.rac-8-[1-azido-2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-7-fluoro-2-methoxy-[1,5]naphthyridine

Starting from intermediate BM.ii (18.85 g) and using procedure N, thetitle intermediate was obtained as an orange oil (22.2 g; contaminatedwith PPh₃O).

¹H NMR (CDCl₃) δ: 8.66 (d, J=1.5 Hz, 1H), 8.20 (d, J=9.1 Hz, 1H), 7.11(d, J=9.1 Hz, 1H), 5.85 (m, 1H), 4.36 (m, 1H), 4.11 (m, 3H), 4.04 (m,1H), 0.87 (s, 9H), 0.06 (d, J=8.8 Hz, 6H).

BM.iv. rac-2-azido-2-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-ethanol

Starting from intermediate BM.iii (20.0 g) and using procedure J, thetitle intermediate was obtained as a yellowish solid (13.76 g; 99%yield).

¹H NMR (CDCl₃) δ: 8.69 (m, 1H), 8.23 (dd, J=9.1, 0.9 Hz, 1H), 7.13 (d,J=9.1 Hz, 1H), 5.92 (dd, J=7.9, 4.7 Hz, 1H), 4.29 (m, 1H), 4.11 (m, 3H),4.06 (d, J=4.4 Hz, 1H), 1.25 (m, 1H).

BM.v.rac-4-azido-3-fluoro-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from intermediate BM.iv (17.75 g) and using procedure H, thetitle intermediate was obtained as an orange solid (7.94 g; 51% yield).

¹H NMR (CDCl₃) δ: 8.45 (m, 1H), 7.88 (m, 1H), 6.84 (m, 1H), 5.66 (dd,J=8.5, 3.5 Hz, 1H), 4.62 (dd, J=13.8, 8.5 Hz, 1H), 4.35 (dd, J=13.8, 3.5Hz, 1H).

BM.vi.(R)-4-amino-3-fluoro-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

A solution of intermediate BM.v (7.93 g) in THF (140 mL) was stirred at60° C. for 3 h in the presence of PPh₃ (9.90 g) and water (6.17 mL). Thereaction mixture was concentrated to dryness and the residue waspurified by CC (DCM/MeOH/NH₄OH 1000:50:4 to 1000:100:8) affording, afterstirring in TBME,(RS)-4-amino-3-fluoro-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one(6.37 g; 91% yield). This racemic material (6.22 g) was separated bypreparative chiral HPLC using a 5 μm (R,R)-Whelk-01 column (50×250 mm)eluting with 4:1 MeCN-EtOH containing 0.1% of diethylamine, witht_(R)=5.21 min for the title compound (compound of Preparation BM) andt_(R)=6.13 min for the optical antipode (compound of Preparation BN).The recovery was 3.00 g (first eluting enantiomer, compound ofPreparation BM, 100% ee) and 2.92 g (second eluting enantiomer, compoundof Preparation BN, 100% ee).

The absolute configuration of the title molecule was determined by X-rayanalysis of the corresponding carboxamide obtained from (S)-mandelicacid.

MS (ESI, m/z): 206.1 [M+H⁺]

Preparation BN:(S)-4-amino-3-fluoro-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

The title compound was obtained as the second eluting enantiomer(t_(R)=6.13 min) at Preparation BM, step BM.vi.

MS (ESI, m/z): 206.1 [M+H⁺].

Preparation BO:rac-1-amino-9-methyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one BO.i.(7-bromo-2-methoxy-quinolin-8-yl)-methanol

A suspension of 7-bromo-8-bromomethyl-2-methoxyquinoline (35.2 g;prepared according to WO 2007/081597) and NaHCO₃ (14.63 g) in acetone(430 mL) and water (430 mL) was refluxed for 6 h. The org. solvent wasremoved under reduced pressure and the aq. layer was extracted twicewith EA. The combined org. layers were sequentially washed with waterand brine and dried over Na₂SO₄. The solvent was removed under reducedpressure and the residue was crystallized from TBDME, affording anoff-white solid (16.01 g; 56% yield).

MS (ESI, m/z): 268.0 [M+H⁺].

BO.ii. 7-bromo-2-methoxy-quinoline-8-carbaldehyde

A solution of oxalyl chloride (5.68 mL) in DCM (265 mL) was cooled to−78° C. and treated dropwise with a solution of DMSO (5.71 mL) in DCM(50 mL). The resulting solution was treated with a solution ofintermediate BO.i (6.00 g) in DCM (50 mL). After stirring for 1 h at−78° C., the reaction mixture was treated with TEA (23.4 mL) in DCM (50mL) and gradually allowed to reach rt. The reaction mixture was treatedwith sat. aq. NaHCO₃ (300 mL) and the org. layer was separated and driedover Na₂SO₄. The solvent was evaporated under reduced pressure and thecrude material was stirred in TBME, affording a yellow solid (4.68 g;79% yield; contaminated by traces of starting material).

MS (ESI, m/z): 266.0 [M+H⁺].

BO.iii. 7-bromo-2-methoxy-8-vinyl-quinoline

Starting from intermediate BO.ii (500 mg) and methyltriphenylphosphoniumbromide (1.01 g) and proceeding in analogy to Preparation Z, step Z.i,the title compound was obtained a colourless solid (411 mg; 83% yield).

MS (ESI, m/z): 264.3 [M+H⁺].

BO.iv. rac-1-(7-bromo-2-methoxy-quinolin-8-yl)-ethane-1,2-diol

Starting from intermediate BO.iii (5.50 g) and proceeding in analogy toPreparation AX, step AX.ii, using however K₂OsO₄/NMO instead of AD-mix βand omitting the use of methylsulfonamide, the title compound wasobtained as a beige solid (5.75 g; 93% yield).

¹H NMR (CDCl3) δ: 8.01 (d, J=9.1 Hz, 1H), 7.58 (m, 1H), 7.50 (m, 1H),6.97 (m, 1H), 5.53 (m, 1H), 4.07 (m, 3H), 3.91 (m, 2H).

BO.v.rac-1-(7-bromo-2-methoxy-quinolin-8-yl)-2-(tert-butyl-dimethyl-silanyloxy)-ethanol

Starting from intermediate BO.iv (5.71 g) and using procedure M, thetitle compound was obtained as a brown oil (7.79 g; 99% yield).

¹H NMR (CDCl₃) δ: 7.97 (d, J=8.8 Hz, 1H), 7.55 (m, 1H), 7.45 (m, 1H),6.93 (d, J=8.8 Hz, 1H), 5.54 (t, J=5.6 Hz, 1H), 4.12 (m, 1H), 4.04 (s,3H), 3.98 (m, 1H), 0.75 (m, 9H), −0.14 (d, J=0.9 Hz, 6H).

BO.vi.rac-8-[1-azido-2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-7-bromo-2-methoxy-quinoline

Starting from intermediate BO.v (7.75 g) and using Procedure N, thetitle intermediate was obtained as a yellow oil (8.47 g; 100% yield).

MS (ESI, m/z): 437.2 [M+H⁺].

BO.vii.rac-1-(7-bromo-2-methoxy-quinolin-8-yl)-2-(tert-butyl-dimethyl-silanyloxy)-ethylamine

Starting from intermediate BO.vi. (8.45 g) and proceeding in analogy toPreparation BM, step BM.vi, the title intermediate was obtained as ayellow oil (2.60 g; 33% yield).

MS (ESI, m/z): 411.3 [M+H⁺].

BO.viii.rac-[1-(7-bromo-2-methoxy-quinolin-8-yl)-2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-carbamicacid tert-butyl ester

Starting from intermediate BO.vii (2.60 g) and using procedure G, thetitle intermediate was obtained as a yellow oil (3.20 g; 99% yield).

¹H NMR (CDCl₃) δ: 7.95 (d, J=9.1 Hz, 1H), 7.55 (m, 1H), 7.44 (m, 1H),6.92 (d, J=9.1 Hz, 1H), 6.35 (m, 1H), 4.97 (m, 1H), 4.06 (m, 3H), 4.03(m, 1H), 3.74 (m, 1H), 1.25 (m, 9H), 0.75 (s, 9H), −0.11 (s, 6H).

BO.ix.rac-[1-(7-bromo-2-methoxy-quinolin-8-yl)-2-hydroxy-ethyl]-carbamic acidtert-butyl ester

Starting from intermediate BO.viii (3.20 g) and using procedure J, thetitle intermediate was obtained as an off-white solid (1.70 g; 68%yield).

MS (ESI, m/z): 396.9 [M+H⁺].

BO.x.rac-(9-bromo-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamicacid tert-butyl ester

Starting from intermediate BO.ix (400 mg) and using procedure H, thetitle intermediate was obtained as a yellow solid (372 mg; 100% yield).

MS (ESI, m/z): 365.3 [M+H⁺].

BO.xi.rac-(9-methyl-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamicacid tert-butyl ester

A solution of intermediate BO.x (90 mg) in DME (1.5 mL) was treated withtetrakis-(triphenylphosphine)palladium and the solution was purged withN₂. The solution was treated with K₂CO₃ (34 mg), water (0.5 mL) andtrimethylboroxine (25 mg) and further stirred at 80° C. overnight. Thereaction mixture was diluted with water and extracted with EA. The org.layer was sequentially washed with water, brine and dried over MgSO₄.The solvent was removed under reduced pressure and the residue waspurified by CC (EA), affording a colourless solid (82 mg; 100% yield).

MS (ESI, m/z): 301.2 [M+H⁺].

BO.xii. rac-1-amino-9-methyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from intermediate BO.xi. (81 mg) and using procedure B, thetitle compound was obtained as a grey solid (34 mg; 79% yield).

MS (ESI, m/z): 201.5 [M+H⁺].

Preparation BP:rac-4-[2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-butyraldehydeBP.i.rac-6-[6-(tert-butyl-dimethyl-silanyloxy)-2-hydroxy-hexylamino]-4H-benzo[1,4]thiazin-3-one

A solution of 2-[4-[(tert-butyl)dimethylsiloxy]butyl]oxirane (10.0 g)and 6-amino-4H-benzo[1,4]thiazin-3-one (7.81 g; commercial) inEtOH/water (300 mL; 9:1) was refluxed for 2 days. The solvents wereremoved under reduced pressure and the residue was taken up in EA/Hex(1:1; 100 mL) and filtered. The filtrate was concentrated under reducedpressure and purified by CC (EA/Hex; 1:1), affording an orange solid(7.40 g; 42% yield).

MS (ESI, m/z): 411.3 [M+H⁺]

BP.ii.rac-6-{5-[4-(tert-Butyl-dimethyl-silanyloxy)-butyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one

Starting from intermediate BP.i (7.30 g) and using procedure I, thetitle intermediate was obtained as a colourless solid (4.40 g; 79%yield).

MS (ESI, m/z): 437.4 [M+H⁺].

BP.iii.rac-6-[5-(4-hydroxy-butyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-one

Starting from intermediate BP.ii (4.40 g) and using procedure J, thetitle intermediate was obtained as a colourless solid (3.00 g; 92%yield).

MS (ESI, m/z): 323.4 [M+H⁺].

BP.iv.rac-4-[2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-butyraldehyde

Starting from intermediate BP.iii (3.0 g) and using the procedure ofPreparation U, step U.iv, the title intermediate was obtained as acolourless solid (2.30 g; 77% yield).

MS (ESI, m/z): 321.3 [M+H⁺].

Preparation BQ:rac-(1R*,2R*)-1-amino-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylicacid methyl ester BQ.i. (E)-3-(2-methoxy-quinolin-8-yl)-acrylic acidmethyl ester

A solution of 8-bromo-2-methyloxyquinoline (10.0 g), Pd(OAc)₂ (311 mg),P(o-Tol)₃ (1.28 g) in DMF (100 mL) was treated with TEA (17.6 mL) andmethyl acrylate (18.93 mL). The solution was purged 3 times withnitrogen and stirred at 120° C. for 1 h. The reaction mixture wasdiluted with water (200 mL) and extracted with ether/EA. The org. layerwas washed with water (3×200 mL) and brine and dried over MgSO₄. Thesolvent was removed under reduced pressure and the residue was purifiedby CC (Hept/EA 4:1), affording a pale yellow solid (9.34 g; 91% yield).

¹H NMR (CDCl₃) δ: 8.00 (d, J=9.1 Hz, 1H), 7.66 (dd, J=7.9, 1.5 Hz, 1H),7.57 (d, J=6.7 Hz, 1H), 7.36 (m, 1H), 6.92 (d, J=8.8 Hz, 1H), 6.24-6.05(m, 2H), 4.84 (m, 1H), 4.10 (s, 3H), 3.89 (d, J=5.0 Hz, 1H), 3.78 (s,3H), 1.43 (m, 9H).

BQ.ii.(2S*,3R*)-3-tert-butoxycarbonylamino-2-hydroxy-3-(2-methoxy-quinolin-8-yl)-propionicacid methyl ester

A solution of tert-butyl carbamate (7.06 g) in n-propanol (120 mL) wassequentially treated with 0.4M NaOH (218 mL) and tert-butyl hypochlorite(10.6 mL; freshly prepared as described in Org. Lett. (2003), 5(12),2123-2126 (S-2)). The reaction mixture was treated with a solution of(DHQD)₂PHAL (565 mg) and (DHQ)₂PHAL (565 mg) in n-propanol (100 mL) andafter 5 min cooled to 10° C. and sequentially treated with a suspensionof intermediate BQ.i. (7.07 g) in water/n-propanol (1:1; 140 mL) andpotassium osmate(VI) dihydrate (428 mg). After stirring at +10° C. for20 min the reaction mixture was treated with Na₂SO₃ (15 g) and furtherstirred at rt for 10 min. The reaction mixture was extracted with EA andthe org. layer was sequentially washed with 5% aq. K₂CO₃, sat. aq.NaHCO₃ and brine. After drying over MgSO₄ and evaporation of thesolvent, the residue was purified by CC (DCM/MeOH 10-1 containing 1%NH₄OH), affording a pale yellow foam (6.85 g; 63% yield).

MS (ESI, m/z): 377.6 [M+H⁺].

BQ.iii.rac-(1R*,2R*)-1-tert-butoxycarbonylamino-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylicacid methyl ester

Starting from intermediate BQ.ii (7.80 g) and using procedure H, thetitle intermediate was obtained as a colourless solid (6.24 g; 87%yield).

MS (ESI, m/z): 345.5 [M+H⁺].

BQ.iv.rac-(1R*,2R*)-1-amino-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylicacid methyl ester

Starting from intermediate BQ.iii. (1.00 g) and using procedure B, thetitle compound was obtained as a colourless solid (684 mg; 96% yield).

MS (ESI, m/z): 245.2 [M+H⁺].

Preparation BR:rac-(1R*,2R*)-1-amino-2-hydroxymethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-oneBR.i.rac-((1R*,2R*)-2-hydroxymethyl-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamicacid tert-butyl ester

Starting from intermediate BQ.iii (3.20 g) and using procedure A, thetitle intermediate was obtained as a colourless solid (2.67 g; 91%yield).

MS (ESI, m/z): 317.3 [M+H⁺].

BR.ii.rac-(1R*,2R*)-1-amino-2-hydroxymethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from intermediate BR.i (600 mg) and using procedure B, thetitle compound was obtained as a colourless oil (400 mg; 98% yield).

MS (ESI, m/z): 217.3 [M+H⁺].

Preparation BS:rac-(1R*,2R*)-1-amino-2-methoxymethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-oneBS.i.rac-((1R*,2R*)-2-methoxymethyl-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamicacid tert-butyl ester

A solution of intermediate BR.i (400 mg) in THF (anhydrous; 4 mL) wastreated at 0° C. with NaH (60% dispersion in oil; 51 mg). After a fewmin the reaction mixture was treated with MeI (83 μL) and furtherstirred at rt for 30 min. The reaction mixture was treated with sat. aq.NH₄Cl and extracted with EA. The org. layer was washed with water andbrine and dried over MgSO₄. The solvent was evaporated under reducedpressure and the residue was purified by CC (DCM/MeOH/NH₄OH 1000:50:4),affording a pale yellow solid (42 mg; 10% yield).

MS (ESI, m/z): 331.2 [M+H⁺].

BS.ii.rac-(1R*,2R*)-1-amino-2-methoxymethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from intermediate BS.i (42 mg) and using procedure B, the titlecompound was obtained as a pale yellow oil (28 mg; 96% yield).

MS (ESI, m/z): 231.2 [M+H⁺].

Preparation BT:rac-(1R*,2S*)-1-amino-2-methyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-oneBT.i.rac-((1R*,2S*)-2-methyl-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamicacid tert-butyl ester

Starting from intermediate BR.i (800 mg) and using procedure H, theintermediate mesylate was formed and further reacted after usual workup. It was dissolved in DME (45 mL) and refluxed in presence of NaI(1.21 g). After 1.5 h the reaction mixture was treated with Bu₃SnH (3mL) and further refluxed for 3 h. The reaction mixture was diluted inether and stirred in presence of 8% aq. KF for 16 h. The mixture wasfiltered. The two phases were separated and the aq. layer was extractedwith EA. The combined org. layers were washed with water and brine anddried over MgSO₄. The solvents were removed under reduced pressure andthe residue was purified by CC (Hept/EA 1:1), affording a colourlesssolid (476 mg; 63% yield).

MS (ESI, m/z): 301.3 [M+H⁺].

BT.ii.rac-(1R*,2S*)-1-amino-2-methyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from intermediate BT.i (467 mg) and using procedure B, thetitle compound was obtained as a yellow oil (274 mg; 88% yield).

MS (ESI, m/z): 201.3 [M+H⁺].

Preparation BU:rac-(1R*,2R*)-1-amino-2-(1-hydroxy-1-methyl-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-oneBU.i.rac-[(1R*,2R*)-2-(1-hydroxy-1-methyl-ethyl)-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl]-carbamicacid tert-butyl ester

A solution BQ.iii (422 mg) in THF (anhydrous; 8 mL) was treated dropwiseat 0° C. with MeMgBr (1.4M in toluene/THF 3:1; 3.1 mL). After stirring 2h at 0° C., the reaction mixture was allowed to reach rt and treatedwith MeMgBr (1.4M in toluene/THF 3:1; 5 mL). The reaction mixture wasfurther stirred at rt overnight, quenched by the addition of sat. NH₄Clsolution and extracted with EA. The org. layer was sequentially washedwith water and brine and dried over MgSO₄. The solvents were evaporatedunder reduced pressure and the residue was purified by CC(DCM/MeOH/NH₄OH 1000:50:4), affording a pale yellow foam (74 mg; 17%yield).

MS (ESI, m/z): 345.5 [M+H⁺].

BU.ii.rac-(1R*,2R*)-1-amino-2-(1-hydroxy-1-methyl-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from intermediate BU.i (74 mg) and using procedure B, the titlecompound was obtained as a brown oil (22 mg; 42% yield).

MS (ESI, m/z): 245.3 [M+H⁺].

Preparation BV:rac-1-amino-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-9-carbonitrileBV.i.rac-(9-cyano-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamicacid tert-butyl ester

A mixture of intermediate BE.ix (135 mg), Zn(CN)₂ (52 mg) and Pd(PPh₃)₄(21 mg) in DMF (2 mL) was heated at 110° C. overnight under argon in asealed flask. After cooling to rt, the reaction mixture was diluted withwater and extracted with EA. The org. layer was washed with water andbrine and dried over MgSO₄. The solvent was removed under reducedpressure and the residue was triturated in TBME, affording a pinkishsolid (88 mg; 76% yield).

MS (ESI, m/z): 312.3 [M+H⁺].

BV.ii.rac-1-amino-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-9-carbonitrile

Starting from intermediate BV.i (88 mg) and using procedure B, the titlecompound was obtained as a colourless solid (57 mg, 95% yield).

MS (ESI, m/z): 212.1 [M+H⁺].

Preparation BW: methanesulfonic acid(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-ylmethylester BW.i.6-[(R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2-oxo-oxazolidin-3-yl]-4H-pyrido[3,2-b][1,4]thiazin-3-one

Starting from(5R)-5-[[[tert-butyldimethylsilyl]oxy]methyl]-2-oxazolidinone (1.20 g;prepared in according to Org. Letters (2005), 7, 1983-1985) andintermediate BK.ii (867 mg), the title compound was prepared in analogyto the preparation of intermediate BK.iii. After work-up and CC (Hept/EA1:1), a beige solid (1.20 g; 70% yield) was obtained.

¹H NMR (CDCl₃) δ: 7.90 (d, J=8.5 Hz, 1H), 7.80 (s, 1H), 7.60 (d, J=8.5Hz, 1H), 4.67 (m, 1H), 4.11 (m, 2H), 3.90 (m, 1H), 3.78 (m, 1H), 3.48(s, 2H), 0.84 (s, 9H), 0.07 (s, 6H).

BW.ii.6-((R)-5-hydroxymethyl-2-oxo-oxazolidin-3-yl)-4H-pyrido[3,2-b][1,4]thiazin-3-one

Starting from intermediate BW.i (1.20 g) and using procedure J, thetitle compound was obtained as a beige solid (880 mg; 100% yield).

MS (ESI, m/z): 282.3 [M+H⁺].

BW.iii. Methanesulfonic acid(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-ylmethylester

Starting from intermediate BW.ii (850 mg) and using procedure H, thetitle compound was obtained as a beige solid (850 mg; 78% yield).

¹H NMR (DMSO-d₆) δ: 10.88 (s, 1H), 7.79 (m, 1H), 7.66 (m, 1H), 5.00 (m,1H), 4.50 (m, 2H), 4.21 (m, 1H), 3.86 (dd, J=10.5, 6.2 Hz, 1H), 3.51 (s,2H), 3.23 (s, 3H).

Preparation BX: methanesulfonic acid2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylester BX.i.(S)-5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-oxazolidin-2-one

Starting from 2-[2-[[(tert-butyl)dimethylsilyl]oxy]ethyl]-oxirane, (7.00g; prepared according to WO 2007/144423), carbamic acid ethyl ester(1.46 g), 4-nitrobenzoic acid (347 mg), (R,R)-(salen)Co^(II) complex(626 mg) and NaH (1.676 g) and proceeding in analogy to Org. Letters(2005), 7, 1983-1985, the title compound was obtained as a dark orangesolid (880 mg; 11% yield).

¹H NMR (DMSO-d₆) δ: 7.39 (s, 1H), 4.59 (m, 1H), 3.67 (m, 2H), 3.53 (m,1H), 3.13 (m, 1H), 1.79 (m, 2H), 0.85 (s, 9H), 0.02 (s, 6H).

BX.ii.6-{(S)-5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-oxo-oxazolidin-3-yl}-4H-pyrido[3,2-b][1,4]thiazin-3-one

Starting from intermediate BX.i (880 mg) and intermediate BK.ii (720mg), the title compound was prepared in analogy to the preparation ofintermediate BK.iii. After work-up and CC (Hept/EA 1:1), a beige solid(1.00 g; 68% yield) was obtained.

MS (ESI, m/z): 410.4 [M+H⁺].

BX.iii.6-[(S)-5-(2-hydroxy-ethyl)-2-oxo-oxazolidin-3-yl]-4H-pyrido[3,2-b][1,4]thiazin-3-one

Starting from intermediate BX.ii (1.00 g) and using procedure J, thetitle compound was obtained as a colourless solid (640 mg; 89% yield).

MS (ESI, m/z): 296.4.3 [M+H⁺].

BX.iv. Methanesulfonic acid2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylester

Starting from intermediate BX.iii (600 mg) and using procedure H, thetitle compound was obtained as a beige solid (649 mg; 81% yield).

MS (ESI, m/z): 374.4 [M+H⁺].

Preparation BY:rac-1-amino-9-chloro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one BY.i.rac-(9-chloro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamicacid tert-butyl ester

A suspension of intermediate BE.ix (140 mg), CuCl (152 mg) and pyridine(0.5 mL) in dry DMSO was heated at 120° C. for 1 h. After cooling to rt,the mixture was partitioned between 1M HCl and EA. The aq. layer wasextracted with EA and the combined org. layers were sequentially washedwith water, NH₄Cl, NaHCO₃, dried over MgSO₄ and concentrated underreduced pressure. The residue was purified by CC (DCM/MeOH/NH₄OH1000:50:4), affording a pale orange solid (104 mg; 85% yield).

MS (ESI, m/z): 321.5 [M+H⁺].

BY.ii. rac-1-amino-9-chloro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from intermediate BY.i (90 mg) and using procedure B, the titlecompound was obtained as an off-white solid (55 mg, 89% yield).

MS (ESI, m/z): 221.1 [M+H⁺].

Preparation BZ:rac-1-amino-9-ethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one BZ.i.rac-(4-oxo-9-trimethylsilanylethynyl-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamicacid tert-butyl ester

PdCl₂(PPh₃)₂ (23 mg) and CuI (7.8 mg) were added to a suspension ofintermediate BE.ix (300 mg) in TEA-dioxane (3 mL; 4:1). The reactionmixture was heated to 70° C. and ethynyl-trimethyl-silane (0.14 mL) wasadded in one portion and the reaction mixture was further heated in asealed glass vial at 100° C. for 2 days. After cooling to rt, themixture was partitioned between 1M HCl and DCM. The org. layer wassequentially washed with water, NH₄Cl, and NaHCO₃, dried over MgSO₄ andconcentrated under reduced pressure. The residue was purified by CC(DCM/MeOH/NH₄OH 1000:50.4), affording a beige solid (132 mg; 42% yield).

MS (ESI, m/z): 383.4 [M+H⁺].

BZ.ii.rac-(9-ethynyl-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamicacid tert-butyl ester

A solution of intermediate BZ.i (115 mg) in THF (2 mL) was treated withTBAF (1M in THF; 0.33 mL) at rt. After 15 min, the mixture wasconcentrated, water was added and the mixture was extracted with DCM.The org. layer was dried over MgSO₄, filtered and concentrated. Theresidue was purified by CC (DCM/MeOH/NH₄OH 1000:50:4), affording ayellow solid (82 mg; 88% yield).

MS (ESI, m/z): 311.6 [M+H⁺].

BZ.iii.rac-(9-ethyl-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamicacid tert-butyl ester

A solution of intermediate BZ.ii (40 mg) in MeOH (1 mL) was hydrogenatedover Pd/C for 2 h. The suspension was filtered using a glass fiberfilter. The filter cake was washed with DCM/MeOH and the filtrate wasconcentrated under reduced pressure, affording a pale yellow solid (37mg; 91% yield).

MS (ESI, m/z): 315.3 [M+H⁺].

BZ.iv. rac-1-amino-9-ethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from intermediate BZ.iii. (30 mg) and using procedure B, thetitle compound was obtained as a colourless solid (13 mg, 64% yield).

MS (ESI, m/z): 215.5 [M+H⁺].

Preparation CA:rac-1-amino-9-ethynyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from intermediate BZ.ii (40 mg) and using procedure B, thetitle compound was obtained as a beige solid (20 mg, 74% yield).

MS (ESI, m/z): 211.3 [M+H⁺].

Preparation CB:rac-(1R*,2R*)-1-amino-9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ii]quinoline-2-carboxylicacid methyl ester CB.i.(2S*3R*)-3-tert-butoxycarbonylamino-2-hydroxy-3-(7-fluoro-2-methoxy-quinolin-8-yl)-propionicacid methyl ester

Starting from (E)-3-(7-fluoro-2-methoxy-quinolin-8-yl)-acrylic acidmethyl ester (7.07 g; prepared in analogy to the corresponding n-butylester described in WO 2008/128953) and proceeding in analogy to thepreparation of intermediate BQ.ii, the title compound was obtained as alight yellow semi-solid material (7.621 g; 84% yield).

MS (ESI, m/z): 395.4 [M+H⁺].

CB.ii.rac-(1R*,2R*)-1-tert-butoxycarbonylamino-9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylicacid methyl ester

Starting from intermediate CB.i (4.60 g) and using procedure H, thetitle intermediate was obtained as a beige solid (81 mg; 19% yield).

MS (ESI, m/z): 363.4 [M+H⁺].

CB.iii.rac-(1R*,2R*)-1-amino-9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylicacid methyl ester

Starting from intermediate CB.ii. (100 mg) and using procedure B, thetitle compound was obtained as a colourless solid (58 mg; 80% yield).

¹H NMR (CDCl₃) δ: 7.71 (dd, J=9.4, 0.9 Hz, 1H), 7.49 (m, 1H), 6.92 (m,1H), 6.63 (d, J=9.4 Hz, 1H), 5.02 (m, 2H), 3.83 (d, J=1.2 Hz, 3H).

Preparation CC:rac-(1R*,2R*)-1-amino-9-fluoro-2-hydroxymethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-oneCC.i.rac-((1R*,2R*)-9-fluoro-2-hydroxymethyl-9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamicacid tert-butyl ester

Starting from intermediate CB.ii (200 mg) and using procedure A, thetitle intermediate was obtained as a colourless solid (112 mg; 61%yield).

MS (ESI, m/z): 335.4 [M+H⁺].

CC.ii.rac-(1R*,2R*)-1-amino-9-fluoro-2-hydroxymethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from intermediate CC.i (104 mg) and using procedure B, thetitle compound was obtained as a colourless solid (60 mg; 82% yield).

MS (ESI, m/z): 235.1 [M+H⁺].

Preparation CD:rac-(1R*,2S*)-1-amino-9-fluoro-2-methyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-oneCD.i.rac-((1R*,2S*)-9-fluoro-2-methyl-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-carbamicacid tert-butyl ester

Starting from intermediate CC.i (495 mg) and using procedure H, theintermediate mesylate was formed and further reacted after usualwork-up. It was dissolved in DME (25 mL) and refluxed in presence of Nat(710 mg). After 1.5 h, the reaction mixture was treated with Bu₃SnH(0.96 mL) and further refluxed for 3 h. The reaction mixture was dilutedin ether and stirred in presence of 8% aq. KF for 16 h. The mixture wasfiltered. The two phases were separated and the aq. layer was extractedwith EA. The combined org. layers were washed with water and brine anddried over MgSO₄. The solvents were removed under reduced pressure andthe residue was purified by CC (Hept/EA 1:1 to 0:1), affording acolourless solid (374 mg; 79% yield).

MS (ESI, m/z): 319.3 [M+H⁺].

CD.ii.rac-(1R*,2S*)-1-amino-9-fluoro-2-methyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from intermediate CD.i (370 mg) and using procedure B, thetitle compound was obtained as a colourless solid (198 mg; 78% yield).

MS (ESI, m/z): 218.9 [M+H⁺].

Preparation CE: rac-(1R*,2R*)-methanesulfonic acid1-amino-9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-2-ylmethylester CE.i. rac-(1R*,2R*)-methanesulfonic acid1-tert-butoxycarbonylamino-9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-2-ylmethylester

Starting from intermediate CC.i (200 mg) and using procedure H, thetitle compound was obtained as a yellow foam (285 mg; 100% yield).

MS (ESI, m/z): 413.3 [M+H⁺].

CE.ii. rac-(1R*,2R*)-methanesulfonic acid1-amino-9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-2-ylmethylester

Starting from intermediate CE.i (280 mg) and using procedure B, thetitle compound was obtained as a beige foam (140 mg; 77% yield).

MS (ESI, m/z): 313.5 [M+H⁺].

Preparation CF:(S)-1-amino-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Intermediate C was separated by chiral prep. HPLC (Column: Daicel,ChiralPak IA, 20×250 mm; eluent: 5% EtOH in MeCN+0.1% DEA; flow: 16.00mL/min). The title compound was obtained as the first eluting compound(t_(R)=7.36 min). The absolute stereochemistry was assigned based on theNMR of the corresponding Mosher amide.

MS (ESI, m/z): 205.2 [M+H⁺].

Preparation CG:(R)-1-amino-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Intermediate C was separated by chiral prep. HPLC (Column: Daicel,ChiralPak IA, 20×250 mm; eluent: 5% EtOH in MeCN+0.1% DEA; flow: 16.00mL/min). The title compound was obtained as the second eluting compound(t_(R)=8.94 min). The absolute stereochemistry was assigned based on theNMR of the corresponding Mosher amide.

MS (ESI, m/z): 205.2 [M+H⁺].

Preparation CH: methanesulfonic acid2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylester

This intermediate was prepared in analogy to Preparation BX, steps BX.ito BX.iii, using however the (S,S)-(salen)Co^(II) complex.

The analytical data were identical with those of the compound ofPreparation BX.

Preparation CI:(RS)-6-amino-7-fluoro-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

The title compound was prepared as described in Preparation AD, usinghowever NMO and K₂OsO₄ as dihydroxylating agent (Cha, J. K., Chem. Rev.(1995), 95, 1761-1795) in the first step.

The analytical data were identical with those of the compound ofPreparation AD.

Example 1(1RS)-9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations A and H and using procedureC, the title compound was obtained as a pale yellow solid (39 mg; 18%yield).

¹H NMR (DMSO-d₆) δ: 10.71 (s, 1H), 7.89 (d, J=9.4 Hz, 1H), 7.58 (m, 1H),7.32 (m, 1H), 6.94 (m, 3H), 6.50 (d, J=9.4 Hz, 1H), 4.67 (m, 1H), 4.53(s, 2H), 4.36 (m, 2H), 4.00 (m, 2H), 3.67 (m, 1H), 3.02 (m, 1H), 2.74(m, 3H), 2.04 (m, 1H), 1.81 (m, 2H).

MS (ESI, m/z): 479.3 [M+H⁺].

Example 2(1RS)-9-fluoro-1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations A and I and using procedureC, the title compound was obtained as a pale yellow solid (35 mg; 16%yield).

¹H NMR (DMSO-d₆) δ: 10.71 (s, 1H), 7.88 (d, J=9.4 Hz, 1H), 7.59 (dd,J=8.8, 4.7 Hz, 1H), 7.32 (m, 1H), 6.96 (m, 3H), 6.50 (d, J=9.4 Hz, 1H),4.68 (m, 1H), 4.53 (s, 2H), 4.32 (m, 2H), 4.00 (m, 2H), 3.65 (m, 1H),3.02 (m, 1H), 2.74 (m, 3H), 2.04 (m, 1H), 1.83 (m, 2H).

MS (ESI, m/z): 479.3 [M+H⁺].

Example 3(1RS)-9-fluoro-1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations A and J and using procedureC, the title compound was obtained as an off-white solid (34 mg; 15%yield).

¹H NMR (DMSO-d₆) δ: 10.56 (s, 1H), 7.88 (d, J=9.4 Hz, 1H), 7.59 (m, 1H),7.32 (m, 2H), 7.01 (m, 2H), 6.50 (dd, J=9.7, 0.9 Hz, 1H), 4.69 (m, 1H),4.32 (m, 2H), 4.02 (m, 2H), 3.66 (m, 1H), 3.43 (s, 2H), 3.02 (m, 1H),2.74 (m, 3H), 1.90 (m, 3H).

MS (ESI, m/z): 495.3 [M+H⁺].

Example 4(1RS)-9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations A and K and using procedureD, the title compound was obtained as an off-white solid (79 mg; 35%yield).

¹H NMR (DMSO-d₆) δ: 10.55 (s, 1H), 7.88 (d, J=9.7 Hz, 1H), 7.57 (m, 1H),7.32 (m, 2H), 7.01 (m, 2H), 6.50 (dd, J=9.4, 0.6 Hz, 1H), 4.69 (m, 1H),4.34 (m, 2H), 4.03 (m, 2H), 3.66 (m, 1H), 3.42 (s, 2H), 3.02 (s, 1H),2.72 (m, 3H), 1.99 (m, 1H), 1.84 (m, 2H).

MS (ESI, m/z): 495.3 [M+H⁺].

Example 5(1RS)-9-fluoro-1-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations A and N and using procedureD, the title compound was obtained as a yellow solid (31 mg; 37% yield).

MS (ESI, m/z): 481.1 [M+H⁺].

Example 6(1RS)-9-fluoro-1-({2-[(RS)-3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations A and S and using procedureC, the title compound was obtained as a yellow solid (94 mg; 47% yield).

MS (ESI, m/z): 440.5 [M+H⁺].

Example 7(1RS)-1-(2-{[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-ethyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations B and P and using procedureD, the title compound was obtained as a pale yellow solid (45 mg; 28%yield).

MS (ESI, m/z): 466.2 [M+H⁺].

Example 8(1RS)-9-fluoro-1-(2-{[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations B and O and using procedureD, the title compound was obtained as a yellow solid (50 mg; 29% yield).

MS (ESI, m/z): 495.1 [M+H⁺].

Example 9(1RS)-9-fluoro-1-(2-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations B and Q and using procedureC, the title compound was obtained as a pale yellow solid (47 mg; 20%yield).

MS (ESI, m/z): 479.2 [M+H⁺].

Example 10(1RS)-9-fluoro-1-(2-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations B and N and using procedureD, the title compound was obtained as a pale yellow solid (38 mg; 16%yield).

MS (ESI, m/z): 494.9 [M+H⁺].

Example 11(1RS)-9-fluoro-1-(2-{[(R)-3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations B and R and using procedureD, the title compound was obtained as a yellow solid (29 mg; 19% yield).

MS (ESI, m/z): 440.5 [M+H⁺].

Example 12(1RS)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations C and T and using procedureE, the title compound was obtained as a colourless solid (42 mg; 45%yield).

¹H NMR (CDCl₃) δ: 7.70 (d, J=9.4 Hz, 1H), 7.47 (m, 1H), 7.32 (m, 1H),6.92 (m, 2H), 6.76 (m, 1H), 6.62 (d, J=9.4 Hz, 1H), 4.96 (m, 1H), 4.64(m, 1H), 4.50 (m, 3H), 4.26 (m, 1H), 4.04 (m, 1H), 3.60 (m, 1H), 3.42(m, 2H), 2.73 (m, 2H), 1.76 (m, 4H).

MS (ESI, m/z): 479.2 [M+H⁺].

Example 13(1RS)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations C and U and using procedureE, the title compound was obtained as a pale beige solid (48 mg; 50%yield).

¹H NMR (CDCl₃) δ: 7.69 (d, J=9.7 Hz, 1H), 7.47 (dd, J=8.5, 4.7 Hz, 1H),7.35 (d, J=2.3 Hz, 1H), 7.24 (m, 2H), 6.91 (m, 2H), 6.61 (d, J=9.4 Hz,1H), 4.95 (dd, J=8.2, 3.2 Hz, 1H), 4.65 (m, 1H), 4.49 (dd, J=13.5, 8.2Hz, 1H), 4.26 (dd, J=13.2, 3.5 Hz, 1H), 4.06 (m, 1H), 3.60 (m, 1H), 3.36(s, 2H), 2.73 (m, 2H), 1.77 (m, 5H).

MS (ESI, m/z): 495.0 [M+H⁺].

Example 14(1RS)-9-fluoro-1-{2-[(RS)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations C and M and using procedureC, the title compound was isolated as a pale yellow solid (13 mg; 12%yield).

¹H NMR (CDCl₃) δ: 8.76 (m, 1H), 7.66 (d, J=9.4 Hz, 1H), 7.44 (m, 2H),7.24 (m, 1H), 6.91 (m, 2H), 6.61 (d, J=9.7 Hz, 1H), 4.96 (m, 1H), 4.80(m, 1H), 4.50 (m, 1H), 4.28 (m, 1H), 4.08 (m, 1H), 3.68 (m, 1H), 3.38(s, 2H), 2.94 (m, 2H), 1.97 (m, 3H).

MS (ESI, m/z): 481.1 [M+H⁺].

Example 15(4R)-4-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations V and J and using procedureC, the title compound was obtained as a colourless solid (9 mg; 12%yield).

MS (ESI, m/z): 478.0 [M+H⁺].

Example 16(4RS)-3-fluoro-4-(2-{[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations F and O and using procedureD, the title compound was obtained as a yellow solid (6 mg; 7% yield).

MS (ESI, m/z): 496.3 [M+H⁺].

Example 17(4RS)-3-fluoro-4-(2-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations F and N and using procedureD, the title compound was obtained as a yellow solid (8 mg; 9% yield).

MS (ESI, m/z): 496.4 [M+H⁺].

Example 18(4R)-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the dihydrochloride salt of the compound of Preparation D(112 mg) and the compound of Preparation U (153 mg) and using procedureE, the title compound was obtained as an orange solid (27 mg; 11%yield).

MS (ESI, m/z): 478.1 [M+H⁺].

Example 19(4R)-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the dihydrochloride salt of the compound of Preparation D(78 mg) and the compound of Preparation T (101 mg) and using procedureE, the title compound was obtained as an orange solid (17 mg; 11%yield).

MS (ESI, m/z): 462.1 [M+H⁺].

Example 20(6RS)-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from the compounds of Preparations G (93 mg) and U (153 mg) andusing procedure E, the title compound was obtained as a yellow solid(210 mg; 88% yield).

MS (ESI, m/z): 478.0 [M+H⁺].

Example 21(6RS)-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from the compounds of Preparations G and T and using procedureE, the title compound was obtained as a yellow solid (276 mg; 70%yield).

MS (ESI, m/z): 462.1 [M+H⁺].

Example 22(1RS)-9-fluoro-1-(2-{[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one

The compound of Example 8 was hydrogenated according to procedure F,affording a colourless solid (10 mg; 23% yield).

MS (ESI, m/z): 497.3 [M+H⁺].

Example 23(1RS)-9-fluoro-1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one23.i.rac-(9-fluoro-4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-1-ylmethyl)-carbamicacid tert-butyl ester

A solution of intermediate A.vii of Preparation A (47 mg, 0.15 mmol) inMeOH (5 mL) was hydrogenated over 10% Pd/C (31 mg) for 2 h. The catalystwas filtered off and washed with MeOH. The filtrate was concentrated toafford the title intermediate as a colourless solid (48 mg; 100% yield).

MS (ESI, m/z): 321.3 [M+H⁺].

23.ii.rac-1-aminomethyl-9-fluoro-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from intermediate 23.i and using procedure B, the titleintermediate was obtained as a yellow solid (29 mg; 88% yield).

MS (ESI, m/z): 221.2 [M+H⁺].

23.iii.(1RS)-9-fluoro-1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from intermediate 23.ii and the compound of Preparation L andusing procedure D, the title compound was obtained as a pale brown solid(8 mg; 14% yield).

MS (ESI, m/z): 497.4 [M+H⁺].

Example 24(1RS)-9-fluoro-1-(2-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one

The compound of Example 10 was hydrogenated using procedure F, affordingthe title compound as an off-white solid (8 mg; 16% yield).

MS (ESI, m/z): 497.2 [M+H⁺].

Example 25(1RS)-9-fluoro-1-(2-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one

The compound of Example 9 was hydrogenated using procedure F, affordingthe title compound as a colourless solid (12 mg; 32% yield).

MS (ESI, m/z): 481.2 [M+H⁺].

Example 26(1RS)-1-(2-{[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-ethyl)-9-fluoro-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one

The compound of Example 7 was hydrogenated using procedure F, affordingthe title compound as an off-white solid (21 mg; 52% yield).

MS (ESI, m/z): 468.2 [M+H⁺].

Example 27(1RS)-9-fluoro-1-(2-{[(R)-3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one

The compound of Example 11 was hydrogenated using procedure F, affordingthe title compound as an off-white solid (17 mg; 74% yield).

MS (ESI, m/z): 442.2 [M+H⁺].

Example 28(4RS)-3-fluoro-4-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations E and L and using procedureD, the title compound was obtained as a yellow solid (7 mg; 18% yield).

MS (ESI, m/z): 496.2 [M+H⁺].

Example 29(1RS)-9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one

The compound of Example 4 was hydrogenated using procedure F, affordingthe title compound as a colourless solid (17 mg; 39% yield).

MS (ESI, m/z): 497.2 [M+H⁺].

Example 30(1RS)-9-fluoro-1-({[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations A and O and using procedureD, the title compound was obtained as a yellow solid (49 mg; 37% yield).

MS (ESI, m/z): 481.2 [M+H⁺].

Example 31(1RS)-1-({[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations A and P and using procedureD, the title compound was obtained as a yellow solid (33 mg; 27% yield).

MS (ESI, m/z): 452.2 [M+H⁺].

Example 32(1RS)-9-fluoro-1-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations A and Q and using procedureC, the title compound was obtained as a yellow solid (35 mg; 27% yield).

MS (ESI, m/z): 465.2 [M+H⁺].

Example 33(1RS)-9-fluoro-1-({[(R)-3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations A and R and using procedureD, the title compound was obtained as a yellow solid (17 mg; 15% yield).

MS (ESI, m/z): 426.2 [M+H⁺].

Example 34(RS)-4-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compound of Preparations W and AF and using procedureC, the title compound was obtained as a beige solid (13 mg; 8% yield).

MS (ESI, m/z): 478.0 [M+H⁺].

Example 35(RS)-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations X and U and using procedureE, the title compound was obtained as a beige solid (30 mg; 24% yield).

MS (ESI, m/z): 476.9 [M+H⁺].

Example 36(RS)-1-({[(R)-3-(4-ethoxy-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compound of Preparation A and(5S)-3-(4-ethoxyphenyl)-5-[[(methylsulfonyl)oxy]methyl]-2-oxazolidinone(prepared according to WO 2008/126034) and using procedure C, the titlecompound was obtained as a yellow solid (44 mg; 27% yield).

MS (ESI, m/z): 472.3 [M+H⁺].

Example 37(RS)-9-fluoro-1-({[(R)-2-oxo-3-(4-propyl-phenyl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations A and AG and using procedureC, the title compound was obtained as a yellow solid (46 mg; 29% yield).

MS (ESI, m/z): 436.1 [M+H⁺].

Example 38(RS)-1-({[(R)-3-(4-butyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations A and AH and using procedureC, the title compound was obtained as a yellow solid (36 mg; 22% yield).

MS (ESI, m/z): 450.1 [M+H⁺].

Example 39(S)-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations Y and U and using procedureE, the title compound was obtained as a beige solid (90 mg; 23% yield).

MS (ESI, m/z): 477.9 [M+H⁺].

Example 40(S)-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations Y and T and using procedureE, the title compound was obtained as a beige foam (55 mg; 15% yield).

MS (ESI, m/z): 461.9 [M+H⁺].

Example 41(S)-4-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations Y and AI and using procedureC, the title compound was obtained as a yellow solid (10 mg; 2% yield).

MS (ESI, m/z): 464.1 [M+H⁺].

Example 42(RS)-1-({2-[(RS)-3-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations A and AJ and using procedureC, the title compound was obtained as a yellow solid (48 mg; 34% yield).

MS (ESI, m/z): 467.1 [M+H⁺].

Example 43(RS)-1-({2-[(RS)-3-(2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-6-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations A and AK and using procedureC, the title compound was obtained as a yellow foam (42 mg; 30% yield).

MS (ESI, m/z): 467.1 [M+H⁺].

Example 44(RS)-1-({2-[(R)-3-(4-ethoxy-phenyl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations A and AL and using procedureC, the title compound was obtained as a yellow foam (20 mg; 14% yield).

¹H NMR (CDCl₃) δ: 7.65 (dd, J=9.4, 1.5 Hz, 1H), 7.38 (m, 3H), 6.87 (m,3H), 6.60 (d, J=9.7 Hz, 1H), 4.70 (m, 1H), 4.44 (m, 2H), 4.01 (m, 4H),3.61 (td, J=9.1, 7.3 Hz, 1H), 3.14 (m, 1H), 2.90 (m, 3H), 1.92 (m, 2H),1.39 (t, J=6.7 Hz, 3H).

MS (ESI, m/z): 452.1 [M+H⁺].

Example 45(RS)-9-fluoro-1-({2-[(R)-2-oxo-3-(4-propyl-phenyl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations A and AM and using procedureC, the title compound was obtained as a yellow foam (24 mg; 17% yield).

¹H NMR (CDCl₃) δ: 7.65 (dd, J=9.7, 1.5 Hz, 1H), 7.39 (m, 3H), 7.16 (d,J=8.5 Hz, 2H), 6.87 (td, J=9.1, 1.8 Hz, 1H), 6.60 (d, J=9.4 Hz, 1H),4.72 (m, 1H), 4.44 (m, 2H), 4.02 (m, 2H), 3.64 (m, 1H), 3.14 (m, 1H),2.90 (m, 3H), 2.55 (m, 2H), 1.91 (m, 2H), 1.61 (m, 2H), 0.92 (t, J=7.3Hz, 3H).

MS (ESI, m/z): 450.1 [M+H⁺].

Example 46(RS)-1-({2-[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations A and AN and using procedureC, the title compound was obtained as an off-white solid (32 mg; 21%yield).

¹H NMR (CDCl₃) δ: 7.64 (dd, J=9.4, 1.2 Hz, 1H), 7.38 (dd, J=8.8, 4.7 Hz,1H), 7.03 (t, J=2.3 Hz, 1H), 6.89 (m, 3H), 6.58 (d, J=9.4 Hz, 1H), 4.68(m, 1H), 4.48 (m, 1H), 4.36 (m, 1H), 4.22 (m, 4H), 3.97 (m, 2H), 3.56(m, 1H), 3.12 (m, 1H), 2.88 (m, 3H), 1.90 (m, 2H).

MS (ESI, m/z): 466.0 [M+H⁺].

Example 47(RS)-9-fluoro-1-({2-[(RS)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations A and AO and using procedureC, the intermediate(RS)-9-fluoro-1-[(2-{3-[(RS)-4-(4-methoxy-benzyl)-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl]-2-oxo-oxazolidin-5-yl}-ethylamino)-methyl]-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-onewas obtained as a yellowish foam (148 mg, 36% yield). Said intermediatewas further treated with TFA (4 mL) at reflux for 3 days. The solventwas removed under reduced pressure and the residue was partitionedbetween DCM and aq. NH₄OH. The org. phase was washed with water andbrine and dried over MgSO₄. The residue was purified by CC (EA/MeOH 9:1containing 1% NH₄OH), affording, after trituration in ether/MeOH, abeige solid (55 mg; 17% yield).

MS (ESI, m/z): 480.0 [M+H⁺].

Example 48(S)-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from the compounds of Preparations Z and U and using procedureE, the title compound was obtained as a beige solid (135 mg; 53% yield).

¹H NMR (DMSO d6) δ: 10.54 (s, 1H), 8.17 (s, 1H), 7.70 (d, J=7.9 Hz, 1H),7.60 (d, J=7.3 Hz, 1H), 7.31 (m, 3H), 7.06 (dd, J=8.5, 2.3 Hz, 1H), 4.70(m, 2H), 4.44 (m, 1H), 4.07 (m, 2H), 3.62 (dd, J=8.8, 7.3 Hz, 1H), 3.41(s, 2H), 2.63 (m, 2H), 1.76 (m, 2H), 1.53 (m, 2H).

Examples 49 and 50(S)-9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-oneand(R)-9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations A and AI and using procedureC, the title compounds were obtained as a light yellow solid (466 mg,26%, mixture of diastereoisomers; MS (ESI, m/z): 495.1 [M+H⁺]). Thismixture (75 mg) was separated on a chiral HPLC column (ChiralPak IA,4.6×250 mm, 5 μm; eluents: MeCN and EtOH containing 0.1% of DEA)affording the corresponding diastereoisomers:

First eluting compound (27 mg): ¹H NMR (CDCl₃) δ: 7.69 (d, J=9.4 Hz,1H), 7.41 (dd, J=8.5, 4.4 Hz, 1H), 7.23 (m, 1H), 7.12 (m, 2H), 6.89 (t,J=9.1 Hz, 1H), 6.62 (d, J=9.7 Hz, 1H), 4.71 (m, 1H), 4.45 (m, 2H), 4.03(m, 2H), 3.62 (m, 2H), 3.34 (s, 2H), 2.95 (m, 3H), 2.00 (m, 1H), 1.78(m, 1H).

Second eluting compound (20 mg): ¹H NMR (CDCl₃) δ: 7.69 (d, J=9.4 Hz,1H), 7.41 (dd, J=8.8, 4.4 Hz, 1H), 7.22 (m, 2H), 7.08 (dd, J=8.5, 2.3Hz, 1H), 6.89 (t, J=9.1 Hz, 1H), 6.60 (d, J=9.4 Hz, 1H), 4.62 (m, 1H),4.48 (m, 1H), 4.35 (m, 1H), 3.96 (m, 2H), 3.71 (m, 1H), 3.34 (s, 2H),3.10 (dd, J=12.0, 4.4 Hz, 1H), 2.88 (m, 3H), 1.91 (m, 2H).

Example 51(RS)-9-fluoro-1-({3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations A and U and using procedureE, the title compound was obtained as a light yellow foam (69 mg; 59%yield).

MS (ESI, m/z): 509.2 [M+H⁺].

Example 52(RS)-9-fluoro-1-({3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations A and T and using procedureE, the title compound was obtained as a light yellow foam (60 mg; 53%yield).

MS (ESI, m/z): 493.2 [M+H⁺].

Example 53(RS)-1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations AB and AF and usingprocedure C, the title compound was obtained as a light yellow foam (10mg; 8% yield).

MS (ESI, m/z): 476.9 [M+H⁺].

Example 54(S)-6-{2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from the compounds of Preparations Z and J and using procedureC, the title compound was obtained as an orange solid (30 mg, 14%yield).

MS (ESI, m/z): 464.1 [M+H⁺].

Example 55(S)-6-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from the compounds of Preparation Z and intermediate K.iv andusing procedure C, the title compound was obtained as an orange solid(50 mg; 20% yield).

MS (ESI, m/z): 464.3 [M+H⁺].

Example 56(RS)-6-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from the compounds of Preparations AC and AI and usingprocedure C, the title compound was obtained as a yellow foam (98 mg;28% yield).

MS (ESI, m/z): 477.9 [M+H⁺].

Example 57(S)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from the compounds of Preparations AD and T and using procedureE, the title compound was obtained as a colourless solid (70 mg; 29%yield).

MS (ESI, m/z): 480.1 [M+H⁺].

Example 58(S)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from the compounds of Preparations AD and U and using procedureE, the title compound was obtained as a colourless solid (85 mg; 34%yield).

MS (ESI, m/z): 469.1 [M+H⁺].

Example 59(RS)-9-fluoro-1-{2-[(R)-2-oxo-3-(4-propyl-phenyl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations C and AM and using procedureC, the title compound was obtained as a yellow solid (46 mg; 31% yield).

¹H NMR (CDCl₃) δ: 7.68 (dd, J=9.4, 0.9 Hz, 1H), 7.45 (m, 3H), 7.17 (d,J=8.2 Hz, 2H), 6.92 (t, J=8.8 Hz, 1H), 6.61 (d, J=9.4 Hz, 1H), 4.99 (m,1H), 4.78 (m, 1H), 4.52 (m, 1H), 4.31 (dd, J=13.2, 3.2 Hz, 1H), 4.10 (t,J=8.5 Hz, 1H), 3.69 (m, 1H), 2.95 (m, 2H), 2.56 (m, 2H), 2.02 (m, 2H),1.62 (m, 2H), 0.92 (t, J=7.3 Hz, 3H).

MS (ESI, m/z): 436.2 [M+H⁺].

Example 60(RS)-1-({2-[(S)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-methyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations A and AQ and using procedureC, the title compound was obtained as a yellow foam (29 mg; 34% yield).

¹H NMR (CDCl₃) δ: 7.65 (dd, J=9.7, 0.9 Hz, 1H), 7.39 (dd, J=8.8, 4.7 Hz,1H), 7.02 (t, J=2.1 Hz, 1H), 6.87 (m, 3H), 6.58 (d, J=9.4 Hz, 1H), 4.70(m, 1H), 4.44 (m, 2H), 4.22 (m, 4H), 3.98 (m, 2H), 3.58 (m, 2H), 3.15(m, 1H), 2.91 (m, 3H), 1.92 (m, 2H).

MS (ESI, m/z): 466.2 [M+H⁺].

Example 61(RS)-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations AE and AI and usingprocedure C, the title compound was obtained as a beige solid (110 mg;46% yield).

¹H NMR (DMSO d6) δ: 10.58 (s, 1H), 7.90 (d, J=9.7 Hz, 1H), 7.54 (m, 2H),7.32 (m, 2H), 7.18 (t, J=7.9 Hz, 1H), 7.08 (m, 1H), 6.55 (d, J=9.7 Hz,1H), 4.81 (m, 1H), 4.39 (m, 2H), 4.08 (m, 3H), 3.72 (m, 1H), 3.42 (s,3H), 3.05 (m, 4H), 2.12 (m, 2H).

MS (ESI, m/z): 476.8 [M+H⁺].

Example 62(RS)-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations AE and H and using procedureC, the title compound was obtained as a beige solid (90 mg; 39% yield).

MS (ESI, m/z): 460.9 [M+H⁺].

Example 63(RS)-1-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations AE and N and using procedureD, the title compound was obtained as a beige solid (44 mg; 19% yield).

MS (ESI, m/z): 462.9 [M+H⁺].

Example 64(R)-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from the compounds of Preparations AA and U and using procedureE, the title compound was obtained as an orange solid (100 mg; 42%yield).

MS (ESI, m/z): 477.8 [M+H⁺].

Example 65(R)-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from the compounds of Preparations AA and T and using procedureE, the title compound was obtained as an orange solid (140 mg; 61%yield).

MS (ESI, m/z): 461.9 [M+H⁺].

Example 66(S)-7-fluoro-6-((2-hydroxy-ethyl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from the compound of Example 58 and(tert-butyldimethylsilyloxy)-acetaldehyde and using procedure E,followed by treatment of the intermediate thus obtained with aq. TFA(50%; 2 mL), the title compound was obtained as a colourless foam (45mg; 40% yield).

MS (ESI, m/z): 539.9 [M+H⁺].

Example 67(S)-7-fluoro-6-((2-hydroxy-ethyl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from the compound of Example 57 and(tert-butyldimethylsilyloxy)-acetaldehyde and using procedure E,followed by treatment of the intermediate thus obtained with aq. TFA(50%; 2 mL), the title compound was obtained as a colourless foam (80mg; 45% yield).

MS (ESI, m/z): 523.9 [M+H⁺].

Example 68(RS)-9-fluoro-1-(2-{(3-hydroxy-propyl)-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one68.i.(RS)-1-(2-{[3-(tert-butyl-dimethyl-silanyloxy)-propyl]-[2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compound of Example 10 and3-(tert-butyldimethylsilyloxy)-propionaldehyde and using procedure E,the title compound was obtained as a colourless solid (101 mg; 75%yield).

MS (ESI, m/z): 667.4 [M+H⁺].

68.ii.(RS)-9-fluoro-1-(2-{(3-hydroxy-propyl)-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from intermediate 68.i and using procedure J, the titlecompound was obtained as an off-white solid (70 mg; 87% yield).

MS (ESI, m/z): 553.2 [M+H⁺].

Example 69(RS)-9-fluoro-1-(2-{(2-hydroxy-ethyl)-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one69.i.(RS)-1-(2-{[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-[2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compound of Example 10 andtert-butyldimethylsilyloxy-acetaldehyde and using procedure E, the titlecompound was obtained as a colourless solid (100 mg; 76% yield).

MS (ESI, m/z): 653.4 [M+H⁺].

69.ii.(RS)-9-fluoro-1-(2-{(2-hydroxy-ethyl)-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-ethyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from intermediate 69.i and using procedure J, the titlecompound was obtained as an off-white solid (54 mg; 69% yield).

MS (ESI, m/z): 539.2 [M+H⁺].

Example 70(RS)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations C and AR and using procedureE, the title compound was obtained as a colourless solid (175 mg; 73%yield).

MS (ESI, m/z): 480.0 [M+H⁺].

Example 71(S)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from the compounds of Preparations AD and AR and usingprocedure E, the title compound was obtained as a colourless solid (87mg; 36% yield).

MS (ESI, m/z): 481.1 [M+H⁺].

Example 72(S)-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations AS and U and using procedureE, the title compound was obtained as a colourless solid (223 mg; 72%yield).

MS (ESI, m/z): 477.2 [M+H⁺].

Example 73(S)-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations AS and T and using procedureE, the title compound was obtained as a colourless solid (259 mg; 87%yield).

MS (ESI, m/z): 461.2 [M+H⁺].

Example 74(S)-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations AS and AR and usingprocedure E, the title compound was obtained as a colourless solid (190mg; 83% yield).

MS (ESI, m/z): 462.2 [M+H⁺].

Example 75(R)-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from the compounds of Preparations AA and AR and usingprocedure E, the title compound was obtained as an orange solid (54 mg;23% yield).

MS (ESI, m/z): 463.0 [M+H⁺].

Example 76(S)-4-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations AT and J and using procedureC, the title compound was obtained as a pale yellow solid (24 mg; 7%yield).

¹H NMR (DMSO-d₆) δ: 10.54 (s, 1H), 8.44 (d, J=4.4 Hz, 1H), 7.94 (d,J=9.7 Hz, 1H), 7.52 (dd, J=4.4, 0.6 Hz, 1H), 7.31 (m, 2H), 7.04 (m, 1H),6.77 (d, J=9.7 Hz, 1H), 4.74 (m, 1H), 4.38 (m, 1H), 4.10 (m, 2H), 3.90(m, 1H), 3.66 (m, 1H), 3.42 (s, 2H), 2.90 (m, 2H), 2.69 (m, 2H), 1.86(m, 2H).

MS (ESI, m/z): 478.2 [M+H⁺].

Example 77(S)-4-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations AT and K and using procedureD, the title compound was obtained as a beige solid (25 mg; 7% yield).

MS (ESI, m/z): 478.2 [M+H⁺].

Example 78(R)-4-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations V and K and using procedureD, the title compound was obtained as a pale yellow solid (150 mg, 42%yield).

MS (ESI, m/z): 478.2 [M+H⁺].

Example 79(S)-7-fluoro-6-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from the compounds of Preparations AD and AU and usingprocedure E, the title compound was obtained as a pale yellow foam (195mg; 79% yield).

¹H NMR (DMSO-d₆) δ: 10.53 (s, 1H), 8.13 (m, 1H), 7.76 (dd, J=8.8, 4.1Hz, 1H), 7.34 (d, J=2.3 Hz, 1H), 7.29 (d, J=8.5 Hz, 1H), 7.10 (m, 2H),4.87 (m, 1H), 4.65 (m, 1H), 4.44 (dd, J=12.9, 8.2 Hz, 1H), 4.08 (m, 2H),3.62 (dd, J=8.8, 7.0 Hz, 1H), 3.41 (s, 2H), 2.60 (m, 2H), 1.74 (m, 2H),1.74 (m, 2H).

Example 80(S)-7-fluoro-6-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from the compounds of Preparations AD and AV and usingprocedure E, the title compound was obtained as a pale yellow solid (215mg; 90% yield).

¹H NMR (DMSO-d₆) δ: 10.69 (s, 1H), 8.13 (s, 1H), 7.76 (dd, J=8.8, 4.4Hz, 1H), 7.31 (d, J=2.3 Hz, 1H), 7.13 (t, J=9.1 Hz, 1H), 6.91 (m, 2H),4.51 (s, 2H), 4.43 (m, 1H), 4.07 (m, 2H), 2.60 (m, 2H), 1.75 (m, 2H),1.55 (m, 2H).

Example 81(RS)-1-({[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations AE and O and using procedureD, the title compound was obtained as a pale yellow solid (42 mg; 18%yield).

MS (ESI, m/z): 463.2 [M+H⁺].

Example 82(RS)-1-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations AE and Q and using procedureC, the title compound was obtained as a beige solid (65 mg; 29% yield).

MS (ESI, m/z): 447.3 [M+H⁺].

Example 83(RS)-1-({3-[(RS)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations AE and AW and usingprocedure C, the title compound was obtained as a beige solid (40 mg;16% yield).

MS (ESI, m/z): 490.9 [M+H⁺].

Example 84(RS)-3-fluoro-4-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compound of Preparation AX and intermediate K.iv andusing procedure C, the title compound was obtained as a light brownsolid (4 mg; 3% yield).

MS (ESI, m/z): 482.2 [M+H⁺].

Example 85(S)-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations AS and AU and usingprocedure E, the title compound was obtained as an off-white solid (182mg; 77% yield).

MS (ESI, m/z): 476.9 [M+H⁺].

Example 86(S)-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations AS and AV and usingprocedure E, the title compound was obtained as an off-white solid (167mg; 72% yield).

MS (ESI, m/z): 460.9 [M+H⁺].

Example 87(S)-1-{2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations AS and J and using procedureC, the title compound was obtained as a light brown solid (82 mg; 27%yield).

MS (ESI, m/z): 462.9 [M+H⁺].

Example 88(S)-1-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compound of Preparation AS and intermediate K.iv andusing procedure C, the title compound was obtained as a light brownsolid (99 mg; 33% yield).

MS (ESI, m/z): 463.0 [M+H⁺].

Example 89(S)-1-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations AS and AY and usingprocedure C, the title compound was obtained as a light brown solid (76mg; 26% yield).

MS (ESI, m/z): 447.0 [M+H⁺].

Example 90(RS)-9-fluoro-1-[((3-hydroxy-propyl)-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl}-amino)-methyl]-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one90.i.(RS)-1-[([3-(tert-butyl-dimethyl-silanyloxy)-propy]-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl}-amino)-methyl]-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compound of Example 4 and3-(tert-butyldimethylsilyloxy)-propionaldehyde and using procedure E,the title compound was obtained as a yellow foam (82 mg; 87% yield).

MS (ESI, m/z): 667.4 [M+H⁺].

90.ii.(RS)-9-fluoro-1-[((3-hydroxy-propyl)-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl}-amino)-methyl]-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from intermediate 90.i and using procedure J, the titlecompound was obtained as a light yellow foam (46 mg; 68% yield).

MS (ESI, m/z): 553.2 [M+H⁺].

Example 91(RS)-9-fluoro-1-[((2-hydroxy-ethyl)-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl}-amino)-methyl]-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one91.i.(RS)-1-[([2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl}-amino)-methyl]-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compound of Example 4 andtert-butyldimethylsilyloxy-acetaldehyde and using procedure E, the titlecompound was obtained as a yellow foam (55 mg; 59% yield).

MS (ESI, m/z): 653.4 [M+H⁺].

91.ii.(RS)-9-fluoro-1-[((2-hydroxy-ethyl)-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl}-amino)-methyl]-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from intermediate 91.i and using procedure J, the titlecompound was obtained as an off-white foam (25 mg; 55% yield).

MS (ESI, m/z): 539.2 [M+H⁺].

Example 92(RS)-9-fluoro-1-((3-hydroxy-propyl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one92.i.(RS)-1-([3-(tert-butyl-dimethyl-silanyloxy)-propyl]-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compound of Example 13 and3-(tert-butyldimethylsilyloxy)-propionaldehyde and using procedure E,the title compound was obtained as a yellow foam (62 mg; 46% yield).

MS (ESI, m/z): 667.4 [M+H⁺].

92.ii.(RS)-9-fluoro-1-((3-hydroxy-propyl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from intermediate 92.i and using procedure J, the titlecompound was obtained as an off-white foam (20 mg; 39% yield).

MS (ESI, m/z): 553.2 [M+H⁺].

Example 93(RS)-9-fluoro-1-((2-hydroxy-ethyl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one93.i.(RS)-1-([2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compound of Example 13 andtert-butyldimethylsilyloxy-acetaldehyde and using procedure E, the titlecompound was obtained as a yellow foam (57 mg; 43% yield).

MS (ESI, m/z): 653.4 [M+H⁺].

93.ii.(RS)-9-fluoro-1-((2-hydroxy-ethyl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from intermediate 93.i and using procedure J, the titlecompound was obtained as a yellowish foam (15 mg; 32% yield).

MS (ESI, m/z): 539.2 [M+H⁺].

Example 94(RS)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations AX and U and using procedureE, the title compound was obtained as a light yellow solid (44 mg; 36%yield).

MS (ESI, m/z): 496.2 [M+H⁺].

Example 95(RS)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations AX and T and using procedureE, the title compound was obtained as a light yellow foam (43 mg; 37%yield).

MS (ESI, m/z): 480.2 [M+H⁺].

Example 96(RS)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations AX and AU and usingprocedure E, the title compound was obtained as an off-white foam (53mg; 44% yield).

MS (ESI, m/z): 496.2 [M+H⁺].

Example 97(RS)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations AX and AV and usingprocedure E, the title compound was obtained as a light yellow foam (44mg; 38% yield).

MS (ESI, m/z): 480.2 [M+H⁺].

Example 98(RS)-3-fluoro-4-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations E and S and using procedureC, the title compound was obtained as a yellow foam (12 mg; 6% yield).

MS (ESI, m/z): 466.2 [M+H⁺].

Example 99(RS)-3-fluoro-4-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations E and AI and using procedureC, the title compound was obtained as a yellow solid (48 mg; 21% yield).

MS (ESI, m/z): 496.2 [M+H⁺].

Example 100(RS)-3-fluoro-4-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations E and N and using procedureD, the title compound was obtained as a yellow foam (27 mg; 12% yield).

MS (ESI, m/z): 482.2 [M+H⁺].

Example 101(RS)-3-fluoro-4-({[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations E and O and using procedureD, the title compound was obtained as a yellow foam (19 mg; 9% yield).

MS (ESI, m/z): 482.2 [M+H⁺].

Example 102(RS)-3-fluoro-4-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations E and H and using procedureC, the title compound was obtained as a yellow foam (15 mg; 7% yield).

MS (ESI, m/z): 480.2 [M+H⁺].

Example 103(RS)-3-fluoro-4-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations E and I and using procedureC, the title compound was obtained as a yellow solid (16 mg; 11% yield).

MS (ESI, m/z): 480.2 [M+H⁺].

Example 104(R)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from the compounds of Preparations AZ and T and using procedureE, the title compound was obtained as a beige solid (97 mg; 40% yield).

MS (ESI, m/z): 480.2 [M+H⁺].

Example 105(R)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from the compounds of Preparations AZ and U and using procedureE, the title compound was obtained as a beige solid (81 mg; 32% yield).

MS (ESI, m/z): 496.2 [M+H⁺].

Example 106(RS)-6-({[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from the compounds of Preparations AC and O and using procedureD, the title compound was obtained as a beige solid (158 mg; 31% yield).

MS (ESI, m/z): 464.2 [M+H⁺].

Example 107(RS)-1-{2-[(S)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations C and AQ and using procedureC, the title compound was obtained as a light brown solid (20 mg; 23%yield).

MS (ESI, m/z): 452.2 [M+H⁺].

Example 108(RS)—N—((S)-9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-3-hydroxy-3-[(RS)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propionamide108.i.(RS)-3-(tert-butyl-dimethyl-silanyloxy)-(3RS)-[2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propionicacid

Starting from a solution of intermediate BA.iii (400 mg; see PreparationB) in DCM and treating with TFA, the title intermediate was obtained,after aqueous workup and trituration with ether, as a colourless solid(0.2 g, 56% yield).

MS (ESI, m/z): 453.0 [M+H⁺].

108.ii.(RS)—N—((S)-9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-3-hydroxy-3-[(RS)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propionamide

A propylphosphonic anhydride solution (50% in EA, 0.31 ml) was addeddropwise to a solution of the compound of Preparation C (0.1 g),intermediate 108.i (0.22 g) and DIPEA (0.26 mL) in DMF (4 mL). Themixture was stirred at rt for 1 h and partitioned between water and EA.The org. phase was washed with dilute HCl and brine, dried over MgSO₄and concentrated. Purification of the crude using CC (EA/MeOH 19:1) gavea mixture of diastereomeric compounds (ratio and relativestereochemistry was not elucidated) as a colourless solid (245 mg). Thisintermediate was treated with HCl in MeOH (1.25/14), stirred at rt for 1h, concentrated in vacuo, partitioned between EA and a bicarbonatesolution. The product precipitated out of this mixture, was filtered offand dried under HV to give the title compound as a colourless solid (20mg, mixture of diastereomers).

MS (ESI, m/z): 525.1 [M+H⁺].

Example 109(R)-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations BC and U and using procedureE, the title compound was obtained as a colourless solid (96 mg; 67%yield).

MS (ESI, m/z): 477.2 [M+H⁺].

Example 110(RS)-6-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from the compounds of Preparations AC and N and using procedureD, the title compound was obtained as a colourless solid (15 mg; 3%yield).

MS (ESI, m/z): 464.2 [M+H⁺].

Example 111(R)-7-fluoro-2-methoxy-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from the compounds of Preparations BB and T and using procedureE, the title compound was obtained as a colourless solid (100 mg; 39%yield).

MS (ESI, m/z): 510.2 [M+H⁺].

Example 112(R)-7-fluoro-2-methoxy-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from the compounds of Preparations BB and U and using procedureE, the title compound was obtained as a colourless solid (75 mg; 28%yield).

MS (ESI, m/z): 526.2 [M+H⁺].

Example 113(1RS)-9-fluoro-1-{(3RS)-3-hydroxy-3-[(5RS)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one113.i.3-(tert-butyl-dimethyl-silanyloxy)-3-[2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propionaldehyde(mixture of diastereomers)

To a solution of the compound of Preparation BA (0.2 g) and DIPEA (0.23mL) in DCM (5 mL) at rt was added dropwise a solution of SO₃.Pyr complex(0.145 g) in DMSO (0.5 mL) over 2 min. The mixture was stirred at rt for1.5 h and partitioned between water and DCM. The org. phase was washedseveral times with water, dried over MgSO₄ and concentrated. The crudeproduct was used as such in the next step (yield assumed to bequantitative).

MS (ESI, m/z): 437.1 [M+H⁺].

113.ii.(1RS)-9-fluoro-1-{(3RS)-3-hydroxy-3-[(5RS)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compound of Preparation C and intermediate 113.i andusing procedure E followed by TBDMS cleavage using procedure J, thetitle compound was obtained as a yellowish solid (21 mg; 9% yield).

MS (ESI, m/z): 510.6 [M+H⁺].

Example 114(S)-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-one

A solution of the compound of Example 48 (33 mg) in MeOH/DCE (5 mL; 4:1)was treated with NaBH₄ (3 mg) for 30 min then quenched with 1M HCl (1mL) and partitioned between DCM and an aq. NH₄OH solution. The org.layer was washed with water and brine, dried over MgSO₄ and purified byCC (EA/MeOH 19:1 to 9:1 containing 1% NH₄OH) affording a colourlesssolid (26 mg; 78% yield).

MS (ESI, m/z): 480.4 [M+H⁺].

Example 115(RS)-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from the compounds of Preparations G and BK and using procedureE, the title compound was obtained as an orange solid (95 mg, 40%yield).

¹H NMR (DMSO-d₆) δ: 10.82 (s, 1H), 8.17 (s, 1H), 7.77 (m, 1H), 7.68 (m,2H), 7.60 (d, J=7.3 Hz, 1H), 7.31 (dd, J=7.9, 7.3 Hz, 1H), 4.71 (m, 2H),4.44 (m, 1H), 4.19 (m, 1H), 4.05 (dd, J=12.9, 3.8 Hz, 1H), 3.69 (dd,J=10.3, 7.0 Hz, 1H), 3.51 (s, 2H), 2.64 (m, 2H), 1.76 (m, 2H), 1.50 (m,2H).

MS (ESI, m/z): 479.4 [M+H⁺].

Example 116(RS)-9-bromo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations BE and U and using procedureE, the title compound was obtained as a colourless solid (10 mg, 9%yield).

MS (ESI, m/z): 555.2 [M+H⁺].

Example 117(RS)-4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-9-carbonitrile

Starting from the compounds of Preparations BV and U and using procedureE, the title compound was obtained as a colourless solid (14 mg, 21%yield).

MS (ESI, m/z): 502.5 [M+H⁺]

Example 118(RS)-4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-9-carbonitrile

Starting from the compounds of Preparations BV and BK and usingprocedure E, the title compound was obtained as a colourless solid (15mg, 22% yield).

¹H NMR (CDCl₃) δ: 7.83 (dd, J=8.5, 1.2 Hz, 1H), 7.75 (d, J=9.4 Hz, 1H),7.58 (m, 2H), 7.41 (d, J=7.9 Hz, 1H), 6.81 (d, J=9.4 Hz, 1H), 5.02 (m,1H), 4.69 (m, 1H), 4.53 (m, 1H), 4.28 (m, 2H), 3.76 (dd, J=10.5, 7.3 Hz,1H), 3.43 (s, 2H), 2.75 (m, 2H), 1.92 (m, 5H).

MS (ESI, m/z): 503.6 [M+H⁺].

Example 119(R)-4-oxo-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-7-carboxylicacid ethyl ester

Starting from the compounds of Preparations BF and AU and usingprocedure E, the title compound was obtained as a colourless solid (910mg, 66% yield).

MS (ESI, m/z): 549.2 [M+H⁺]

Example 120(R)-7-hydroxymethyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations BG and AU and usingprocedure E, the title compound was obtained as a beige solid (40 mg,16% yield).

MS (ESI, m/z): 507.2 [M+H⁺].

Example 121(R)-4-oxo-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-7-carboxylicacid hydrochloride

A suspension of the compound of Example 119 (100 mg) in 6M HCl (0.6 mL)was stirred at 90° C. for 6 h. The reaction mixture was evaporated underreduced pressure and the residue was taken up in MeOH and collected byfiltration, affording a beige solid (37 mg; 36% yield).

MS (ESI, m/z): 521.5 [M+H⁺].

Example 122(R)-7-dimethylaminomethyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations BH and AU and usingprocedure E, the title compound was obtained as a beige solid (39 mg;30% yield).

MS (ESI, m/z): 534.5 [M+H⁺].

Example 123(R)-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-7-pyrrolidin-1-ylmethyl-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations BI and AU and usingprocedure E, the title compound was obtained as a beige foam (50 mg, 27%yield).

MS (ESI, m/z): 560.6 [M+H⁺].

Example 124(RS)-9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations C and BJ and using procedureE, the title compound was obtained as a colourless foam (87 mg, 60%yield).

MS (ESI, m/z): 480.5 [M+H⁺].

Example 125(RS)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations C and BK and using procedureE, the title compound was obtained as a colourless solid (84 mg, 49%yield).

¹H NMR (CDCl₃) δ: 8.04 (m, 1H), 7.88 (dd, J=8.5, 2.9 Hz, 1H), 7.68 (dd,J=9.4, 1.2 Hz, 1H), 7.60 (dd, J=8.5, 1.5 Hz, 1H), 7.47 (dd, J=8.8, 4.7Hz, 1H), 6.91 (t, J=9.1 Hz, 1H), 6.63 (d, J=9.4 Hz, 1H), 5.00 (m, 1H),4.66 (m, 1H), 4.51 (m, 1H), 4.27 (m, 2H), 3.77 (dt, J=10.3, 6.7 Hz, 1H),3.47 (s, 2H), 2.77 (m, 2H), 1.80 (m, 4H).

MS (ESI, m/z): 496.6 [M+H⁺].

Example 126(RS)-9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations C and BL and using procedureE, the title compound was obtained as a colourless solid (54 mg, 32%yield).

¹H NMR (CDCl₃) δ: 8.03 (m, 1H), 7.88 (dd, J=8.8, 2.9 Hz, 1H), 7.68 (dd,J=9.4, 0.9 Hz, 1H), 7.60 (dd, J=8.5, 1.5 Hz, 1H), 7.47 (dd, J=8.8, 4.7Hz, 1H), 6.91 (t, J=9.1 Hz, 1H), 6.63 (d, J=9.4 Hz, 1H), 5.00 (m, 1H),4.66 (m, 1H), 4.51 (m, 1H), 4.28 (m, 2H), 3.77 (dt, J=10.5, 7.0 Hz, 1H),3.47 (s, 2H), 2.77 (m, 2H), 1.80 (m, 4H).

MS (ESI, m/z): 496.6 [M+H⁺].

Examples 127 and 128(R)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-oneand(S)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

The product of Example 13 was separated by preparative chiral HPLC usinga 5 μm (R,R)-Whelk-01 column (21.1×250 mm) eluting with 1:1 MeCN-EtOHcontaining 0.1% of diethylamine with t_(R)=7.25 min (compound of Example127, 100% ee) and t_(R)=10.26 min (compound of Example 128, 100% ee).

Data Obtained for the Compound of Example 127:

¹H NMR (CDCl₃) δ: 7.69 (d, J=9.7 Hz, 1H), 7.47 (dd, J=8.8, 4.7 Hz, 1H),7.31 (d, J=2.3 Hz, 1H), 7.22 (d, J=8.5 Hz, 1H), 6.91 (m, 2H), 6.60 (d,J=9.4 Hz, 1H), 4.95 (dd, J=8.2, 3.5 Hz, 1H), 4.64 (m, 1H), 4.48 (m, 1H),4.26 (dd, J=13.5, 3.5 Hz, 1H), 4.04 (t, J=8.8 Hz, 1H), 3.59 (dd, J=8.8,7.0 Hz, 1H), 3.34 (s, 2H), 2.73 (m, 2H), 1.76 (m, 4H).

MS (ESI, m/z): 495.3 [M+H⁺].

Data Obtained for the Compound of Example 128:

¹H NMR (CDCl₃) δ: 7.68 (d, J=9.4 Hz, 1H), 7.46 (dd, J=8.5, 4.7 Hz, 1H),7.31 (d, J=2.3 Hz, 1H), 7.21 (d, J=8.5 Hz, 1H), 6.90 (m, 2H), 6.59 (d,J=9.4 Hz, 1H), 4.94 (dd, J=8.2, 2.9 Hz, 1H), 4.62 (m, 1H), 4.47 (dd,J=13.2, 8.2 Hz, 1H), 4.24 (dd, J=13.5, 3.5 Hz, 1H), 4.02 (t, J=8.5 Hz,1H), 3.60 (m, 1H), 3.33 (s, 2H), 2.72 (m, 2H), 1.74 (m, 4H).

MS (ESI, m/z): 495.3 [M+H⁺].

Examples 129 and 130(R)-9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-oneand(S)-9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

First Step:

Starting from the compound of Example 4 and3-(tert-butyldimethylsilyloxy)-propionaldehyde and using procedure E,the title compound was obtained as a yellow foam (82 mg; 87% yield).

MS (ESI, m/z): 667.4 [M+H⁺].

Second Step:

The product from the first step was separated by preparative chiral HPLCusing a 5 μm (R,R)-Whelk-01 column (21.1×250 mm) eluting with 1:1MeCN-EtOH containing 0.1% of diethylamine with t_(R)=7.41 min (compoundof Example 129, 100% ee) and t_(R)=10.35 min (compound of Example 130,100% ee).

Data Obtained for the Compound of Example 129:

¹H NMR (CDCl₃) δ: 7.68 (d, J=9.4 Hz, 1H), 7.46 (dd, J=8.8, 4.7 Hz, 1H),7.30 (d, J=2.1 Hz, 1H), 7.20 (d, J=8.5 Hz, 1H), 6.90 (m, 2H), 6.58 (d,J=9.4 Hz, 1H), 4.94 (dd, J=8.2, 3.2 Hz, 1H), 4.63 (m, 1H), 4.46 (dd,J=13.5, 8.5 Hz, 1H), 4.23 (dd, J=13.5, 3.5 Hz, 1H), 4.02 (t, J=8.5 Hz,1H), 3.58 (dd, J=7.9, 7.0 Hz, 1H), 3.33 (s, 2H), 2.72 (m, 2H), 1.74 (m,4H).

MS (ESI, m/z): 495.4 [M+H⁺].

Data Obtained for the Compound of Example 130:

¹H NMR (CDCl₃) δ: 7.68 (d, J=9.4 Hz, 1H), 7.46 (dd, J=8.8, 4.7 Hz, 1H),7.30 (d, J=2.3 Hz, 1H), 7.21 (d, J=8.5 Hz, 1H), 6.90 (m, 2H), 6.59 (d,J=9.4 Hz, 1H), 4.94 (dd, J=8.5, 3.5 Hz, 1H), 4.64 (m, 1H), 4.47 (m, 1H),4.24 (dd, J=13.2, 3.5 Hz, 1H), 4.03 (t, J=8.5 Hz, 1H), 3.59 (dd, J=8.8,7.0 Hz, 1H), 3.33 (s, 2H), 2.71 (m, 2H), 1.75 (m, 4H).

MS (ESI, m/z): 495.4 [M+H⁺].

Example 131(R)-7-fluoro-6-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from the compounds of Preparations AA and BJ and usingprocedure E, the title compound was obtained as a yellowish solid (61mg, 42% yield).

¹H NMR (DMSO-d6) δ: 11.14 (s, 1H), 8.13 (s, 1H), 7.76 (dd, J=8.8, 4.4Hz, 1H), 7.56 (m, 1H), 7.39 (d, J=8.8 Hz, 1H), 7.13 (t, J=9.1 Hz, 1H),4.66 (s, 1H), 4.58 (s, 3H), 4.44 (m, 1H), 4.18 (m, 1H), 4.08 (dd,J=13.2, 3.2 Hz, 1H), 3.67 (dd, J=10.0, 7.0 Hz, 1H), 2.60 (m, 2H), 1.74(m, 2H), 1.49 (m, 2H).

MS (ESI, m/z): 481.4 [M+H⁺].

Example 132(R)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from the compounds of Preparations AA and BK and usingprocedure E, the title compound was obtained as a colourless solid (50mg, 50% yield).

¹H NMR (DMSO-d6) δ: 10.81 (s, 1H), 8.13 (s, 1H), 7.77 (m, 2H), 7.66 (m,1H), 7.13 (t, J=9.1 Hz, 1H), 4.90 (m, 1H), 4.69 (m, 1H), 4.44 (dd,J=12.9, 8.2 Hz, 1H), 4.19 (m, 1H), 4.08 (m, 1H), 3.68 (dd, J=10.0, 7.0Hz, 1H), 3.51 (s, 2H), 2.60 (dd, J=1.2, 0.6 Hz, 2H), 1.75 (m, 2H), 1.50(m, 2H).

Example 133(R)-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations BC and AU and usingprocedure E, the title compound was obtained as a yellow solid (54 mg,45% yield).

MS (ESI, m/z): 477.2 [M+H⁺].

Example 134(R)-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations BC and AV and usingprocedure E, the title compound was obtained as a colourless solid (80mg, 69% yield).

MS (ESI, m/z): 461.2 [M+H⁺].

Example 135(R)-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations BC and BJ and usingprocedure E, the title compound was obtained as an off-white solid (75mg, 65% yield).

MS (ESI, m/z): 462.1 [M+H⁺].

Example 136(S)-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations AS and BL and usingprocedure E, the title compound was obtained as a beige solid (31 mg,33% yield).

¹H NMR (DMSO-d6) δ: 10.82 (s, 1H), 7.89 (d, J=9.7 Hz, 1H), 7.77 (m, 1H),7.66 (m, 1H), 7.55 (m, 2H), 7.18 (t, J=7.6 Hz, 1H), 6.54 (d, J=9.4 Hz,1H), 4.70 (m, 2H), 4.37 (m, 1H), 4.19 (m, 1H), 4.00 (m, 1H), 3.69 (m,1H), 3.51 (s, 2H), 2.64 (m, 2H), 1.76 (m, 2H), 1.52 (m, 2H).

MS (ESI, m/z): 478.2 [M+H⁺].

Example 137(S)-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations AS and BK and usingprocedure E, the title compound was obtained as an off-white foam (143mg, 60% yield).

MS (ESI, m/z): 478.2 [M+H⁺].

Example 138(R)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations BM and U and using procedureE, the title compound was obtained as an off-white foam (17 mg, 14%yield).

¹H NMR (CDCl₃) δ: 9.04 (s, 1H), 8.36 (s, 1H), 7.87 (m, 1H), 7.41 (d,J=2.1 Hz, 1H), 7.23 (m, 1H), 6.84 (m, 2H), 5.04 (dd, J=8.5, 3.8 Hz, 1H),4.59 (m, 2H), 4.28 (dd, J=13.5, 3.8 Hz, 1H), 4.04 (t, J=8.8 Hz, 1H),3.59 (m, 1H), 3.36 (s, 2H), 2.80 (m, 2H), 1.83 (m, 5H).

MS (ESI, m/z): 496.3 [M+H⁺].

Example 139(R)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations BM and AU and usingprocedure E, the title compound was obtained as a yellowish foam (10 mg,8% yield).

¹H NMR (CDCl₃) δ: 8.37 (s, 1H), 7.90 (m, 1H), 7.32 (d, J=2.6 Hz, 1H),7.24 (m, 2H), 6.90 (m, 1H), 6.82 (d, J=9.7 Hz, 1H), 5.06 (m, 1H), 4.60(m, 2H), 4.30 (m, 1H), 4.05 (t, J=8.8 Hz, 1H), 3.61 (m, 1H), 3.35 (s,2H), 2.81 (m, 2H), 1.79 (m, 4H).

MS (ESI, m/z): 496.6 [M+H⁺].

Example 140(R)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations BM and T and using procedureE, the title compound was obtained as yellowish foam (6 mg, 5%).

¹H NMR (CDCl₃) δ: 8.36 (d, J=1.2 Hz, 1H), 7.89 (d, J=9.7 Hz, 1H), 7.30(d, J=2.6 Hz, 1H), 6.81 (m, 3H), 5.03 (m, 1H), 4.59 (m, 4H), 4.26 (dd,J=13.2, 3.8 Hz, 1H), 4.03 (t, J=8.5 Hz, 1H), 3.58 (m, 1H), 2.77 (m, 2H),1.77 (m, 5H).

MS (ESI, m/z): 480.6 [M+H⁺].

Example 141(R)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations BM and AV and usingprocedure E, the title compound was obtained as a yellowish foam (8 mg,7% yield).

¹H NMR (CDCl₃) δ: 8.37 (d, J=1.5 Hz, 1H), 7.90 (d, J=9.7 Hz, 1H), 7.36(d, J=2.3 Hz, 1H), 6.90 (m, 1H), 6.83 (d, J=9.4 Hz, 1H), 6.73 (dd,J=8.8, 2.6 Hz, 1H), 5.03 (m, 1H), 4.59 (m, 4H), 4.25 (dd, J=13.2, 3.8Hz, 1H), 4.04 (t, J=8.5 Hz, 1H), 3.59 (m, 1H), 2.76 (m, 2H), 1.78 (m,5H).

MS (ESI, m/z): 480.6 [M+H⁺].

Example 142(R)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations BM and BK and usingprocedure E, the title compound was obtained as a yellowish solid (24mg, 20% yield).

¹H NMR (DMSO-d₆) δ: 10.81 (s, 1H), 8.45 (d, J=0.9 Hz, 1H), 7.96 (d,J=9.7 Hz, 1H), 7.77 (m, 1H), 7.66 (m, 1H), 6.75 (d, J=9.7 Hz, 1H), 4.95(m, 1H), 4.70 (m, 1H), 4.44 (dd, J=12.9, 8.5 Hz, 1H), 4.19 (m, 1H), 4.04(dd, J=12.9, 3.5 Hz, 1H), 3.69 (dd, J=10.3, 7.0 Hz, 1H), 3.51 (s, 2H),2.67 (m, 3H), 1.75 (m, 2H), 1.51 (m, 2H).

MS (ESI, m/z): 497.4 [M+H⁺].

Example 143(R)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations BM and BL and usingprocedure E, the title compound was obtained as an off-white solid (26mg, 21% yield).

¹H NMR (DMSO-d₆) δ: 10.81 (s, 1H), 8.45 (d, J=0.6 Hz, 1H), 7.96 (dd,J=9.7, 0.6 Hz, 1H), 7.77 (m, 1H), 7.66 (m, 1H), 6.75 (d, J=9.7 Hz, 1H),4.95 (m, 1H), 4.70 (m, 1H), 4.44 (m, 1H), 4.19 (m, 1H), 4.04 (dd,J=12.6, 3.5 Hz, 1H), 3.69 (m, 1H), 3.51 (s, 3H), 2.67 (m, 3H), 1.76 (m,2H), 1.52 (m, 2H).

MS (ESI, m/z): 497.3 [M+H⁺].

Example 144(R)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations BM and BJ and usingprocedure E, the title compound was obtained as a colourless solid (20mg, 17% yield).

¹H NMR (DMSO-d₆) δ: 11.15 (s, 1H), 8.45 (d, J=1.5 Hz, 1H), 7.96 (d,J=9.7 Hz, 1H), 7.57 (m, 1H), 7.40 (m, 1H), 6.75 (d, J=9.7 Hz, 1H), 4.95(m, 1H), 4.67 (m, 1H), 4.58 (s, 2H), 4.44 (dd, J=12.9, 8.5 Hz, 1H), 4.18(m, 1H), 4.04 (dd, J=12.6, 3.5 Hz, 1H), 3.69 (m, 1H), 2.68 (m, 3H), 1.75(m, 2H), 1.52 (m, 2H).

MS (ESI, m/z): 481.5 [M+H⁺].

Example 145(S)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations BN and U and using procedureE, the title compound was obtained as a yellowish foam (16 mg, 13%yield).

¹H NMR (CDCl₃) δ: 8.37 (d, J=1.2 Hz, 1H), 7.89 (d, J=9.7 Hz, 1H), 7.31(d, J=2.3 Hz, 1H), 7.22 (d, J=8.5 Hz, 1H), 6.91 (dd, J=8.5, 2.3 Hz, 1H),6.81 (d, J=9.7 Hz, 1H), 5.08 (m, 1H), 4.60 (m, 2H), 4.32 (m, 1H), 4.05(m, 1H), 3.60 (m, 1H), 3.34 (s, 2H), 2.83 (m, 2H), 1.85 (m, 4H).

MS (ESI, m/z): 496.5 [M+H⁺].

Example 146(S)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations BN and T and using procedureE, the title compound was obtained as a yellow foam (7 mg, 6% yield).

MS (ESI, m/z): 480.6 [M+H⁺].

Example 147(S)-3-fluoro-4-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations BN and BK and usingprocedure E, the title compound was obtained as a colourless solid (13mg, 11% yield).

¹H NMR (DMSO-d₆) δ: 10.82 (s, 1H), 8.45 (s, 1H), 7.96 (d, J=10.0 Hz,1H), 7.77 (m, 1H), 7.66 (m, 1H), 6.75 (d, J=10.0 Hz, 1H), 4.96 (m, 1H),4.69 (m, 1H), 4.44 (m, 1H), 4.19 (m, 1H), 4.04 (m, 1H), 3.69 (m, 1H),3.50 (s, 2H), 2.66 (m, 2H), 1.75 (m, 2H), 1.51 (m, 2H).

MS (ESI, m/z): 497.6 [M+H⁺].

Example 148(S)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations BN and AU and usingprocedure E, the title compound was obtained as a yellowish foam (30 mg,25% yield).

¹H NMR (CDCl₃) δ: 8.36 (d, J=1.5 Hz, 1H), 7.89 (d, J=10.0 Hz, 1H), 7.32(d, J=2.3 Hz, 1H), 7.22 (d, J=8.5 Hz, 1H), 6.90 (dd, J=8.5, 2.3 Hz, 1H),6.81 (d, J=9.7 Hz, 1H), 5.04 (ddd, J=8.5, 4.1, 0.6 Hz, 1H), 4.59 (m,2H), 4.27 (dd, J=13.2, 3.8 Hz, 1H), 4.05 (m, 1H), 3.60 (dd, J=9.1, 7.3Hz, 1H), 3.35 (s, 2H), 2.79 (m, 2H), 1.78 (m, 5H).

MS (ESI, m/z): 496.6 [M+H⁺].

Example 149(S)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations BN and AV and usingprocedure E, the title compound was obtained as a yellow foam (8 mg, 7%yield).

MS (ESI, m/z): 480.5 [M+H⁺].

Example 150(S)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations BN and BL and usingprocedure E, the title compound was obtained as an orange foam (6 mg, 5%yield).

MS (ESI, m/z): 497.4 [M+H⁺]

Example 151(S)-3-fluoro-4-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

Starting from the compounds of Preparations BN and BJ and usingprocedure E, the title compound was obtained as a yellowish solid (11mg, 9% yield).

¹H NMR (DMSO-d₆) δ: 11.15 (s, 1H), 8.45 (s, 1H), 7.96 (d, J=9.7 Hz, 1H),7.57 (m, 1H), 7.40 (m, 1H), 6.75 (d, J=10.0 Hz, 1H), 4.96 (m, 1H), 4.67(m, 1H), 4.58 (s, 2H), 4.44 (m, 1H), 4.19 (m, 1H), 4.05 (m, 1H), 3.68(m, 1H), 2.66 (m, 2H), 1.76 (m, 2H), 1.51 (m, 3H).

MS (ESI, m/z): 481.5 [M+H⁺].

Example 152(RS)-9-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations BO and U and using procedureE, the title compound was obtained as a colourless solid (32 mg, 38%yield).

MS (ESI, m/z): 491.2 [M+H⁺].

Example 153(RS)-9-fluoro-1-(methyl-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-amino)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

A suspension of the compound of Example 152 (20 mg) in MeOH (2 mL) wastreated with an aq. formaldehyde solution (37%; 16 μL) for 10 min, thentreated with NaBH₃CN (2.5 mg). After 3 h stirring at rt, the reactionmixture was taken up in water and extracted with EA. The org. layer waswashed with water, brine and dried over MgSO₄. The org. layer wasfiltrated and evaporated under reduced pressure and the residue waspurified by CC (DCM/MeOH/NH₄OH 100:50:4), affording a colourless foam (9mg; 44% yield).

¹H NMR (CDCl₃) δ: 8.50 (s, 1H), 7.70 (d, J=9.7 Hz, 1H), 7.48 (dd, J=8.5,4.4 Hz, 1H), 7.40 (d, J=2.1 Hz, 1H), 7.27 (m, 1H), 6.94 (m, 2H), 6.64(d, J=9.4 Hz, 1H), 5.03 (t, J=6.4 Hz, 1H), 4.67 (m, 1H), 4.38 (d, J=6.4Hz, 2H), 4.08 (m, 1H), 3.62 (m, 1H), 3.40 (s, 2H), 2.50 (m, 2H), 2.22(d, J=4.1 Hz, 3H), 1.77 (m, 4H).

MS (ESI, m/z): 509.3 [M+H⁺].

Example 154(RS)-6-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from the compounds of Preparations AC and H and using procedureC, the title compound was obtained as a yellowish foam (82 mg, 35%yield).

MS (ESI, m/z): 462.1 [M+H⁺]

Example 155(RS)-6-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from the compounds of Preparations AC and I and using procedureC, the title compound was obtained as yellow foam (90 mg, 39% yield).

MS (ESI, m/z): 462.1 [M+H⁺].

Example 156(RS)-6-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from the compounds of Preparations AC and J and using procedureC, the title compound was obtained as a brown foam (270 mg, 37% yield).

MS (ESI, m/z): 478.2 [M+H⁺].

Example 157(R)-1-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations BC and H and using procedureC, the title compound was obtained as a yellowish foam (59 mg, 26%yield).

MS (ESI, m/z): 447.2 [M+H⁺].

Example 158(R)-1-{2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations BC and J and using procedureC, the title compound was obtained as a brown foam (81 mg, 35% yield).

MS (ESI, m/z): 463.2 [M+H⁺].

Example 159(RS)-9-fluoro-1-{4-[(RS)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-butylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations C and BP and using procedureE, the title compound was obtained as a colourless foam (84 mg, 55%yield).

MS (ESI, m/z): 509.1 [M+H⁺].

Example 160(S)-7-fluoro-6-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-one

A solution of the compound of Example 79 (42 mg) in DCM/MeOH (2:1; 6 mL)was treated with NaBH₄ (3.2 mg). After 30 min stirring at rt, thereaction mixture was quenched with 1M HCl (1 mL) and partitioned betweenDCM and aq. NH₄OH. The org. layer was washed with water, dried overMgSO₄, concentrated under reduced pressure and purified by CC (EA/MeOH19:1 to 9:1), affording a beige solid (29 mg; 69% yield).

MS (ESI, m/z): 498.2 [M+H⁺].

Example 161(1R,2R)-4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylicacid methyl ester and(1S,2S)-4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylicacid methyl ester

Starting from the compounds of Preparations BQ and U and using procedureE, a mixture of the title compounds was obtained as a yellowish solid(46 mg, 23% yield).

MS (ESI, m/z): 535.6 [M+H⁺].

Example 162(1R,2R)-4-oxo-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylicacid methyl ester and(1S,2S)-4-oxo-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylicacid methyl ester

Starting from the compounds of Preparations BQ and AU and usingprocedure E, a mixture of the title compounds was obtained as acolourless solid (67 mg, 32% yield).

MS (ESI, m/z): 535.7 [M+H⁺].

Example 163(1R,2R)-2-hydroxymethyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-oneand(1S,2S)-2-hydroxymethyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations BR and U and using procedureE, a mixture of the title compounds was obtained as a colourless solid(99 mg, 54% yield).

MS (ESI, m/z): 507.2 [M+H⁺].

Example 164(1R,2R)-2-hydroxymethyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-oneand(1S,2S)-2-hydroxymethyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations BR and AU and usingprocedure E, a mixture of the title compounds was obtained as acolourless solid (110 mg, 60% yield).

MS (ESI, m/z): 507.2 [M+H⁺].

Example 165(1R,2R)-2-methoxymethyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-oneand(1S,2S)-2-methoxymethyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations BS and U and using procedureE, a mixture of the title compounds was obtained as a colourless solid(20 mg, 32% yield).

MS (ESI, m/z): 521.6 [M+H⁺].

Example 166(1R,2S)-2-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-oneand(1S,2R)-2-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations BT and U and using procedureE, a mixture of the title compounds was obtained as a colourless solid(56 mg, 38% yield).

¹H NMR (CDCl₃) δ: 8.57 (s, 1H), 7.71 (dd, J=9.4, 0.6 Hz, 1H), 7.52 (m,2H), 7.33 (m, 1H), 7.23 (m, 2H), 6.99 (m, 1H), 6.69 (dd, J=9.4, 1.5 Hz,1H), 4.82 (d, J=6.4 Hz, 1H), 4.65 (m, 1H), 4.26 (s, 1H), 4.05 (td,J=8.5, 6.2 Hz, 1H), 3.63 (m, 1H), 3.39 (s, 2H), 2.80 (m, 2H), 1.87 (m,5H), 1.56 (d, J=6.7 Hz, 3H).

MS (ESI, m/z): 491.3 [M+H⁺].

Example 167(1R,2S)-2-methyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-oneand(1S,2R)-2-methyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations BT and AU and usingprocedure E, a mixture of the title compounds was obtained as acolourless solid (59 mg, 40% yield).

¹H NMR (CDCl₃) δ: 8.60 (dd, J=2.3, 0.6 Hz, 1H), 7.71 (dd, J=9.4, 0.9 Hz,1H), 7.51 (m, 2H), 7.33 (dd, J=14.4, 2.3 Hz, 1H), 7.24 (m, 2H), 6.98(td, J=8.2, 2.3 Hz, 1H), 6.69 (dd, J=9.4, 1.8 Hz, 1H), 4.80 (dt, J=6.4,1.8 Hz, 1H), 4.64 (m, 1H), 4.24 (s, 1H), 4.05 (td, J=8.5, 5.9 Hz, 1H),3.61 (dd, J=8.8, 7.0 Hz, 1H), 3.39 (s, 2H), 2.80 (m, 2H), 1.79 (m, 5H),1.55 (d, J=6.4 Hz, 3H).

MS (ESI, m/z): 491.3 [M+H⁺].

Example 168(1R,2S)-2-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-oneand(1S,2R)-2-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations BT and BK and usingprocedure E, a mixture of the title compounds was obtained as acolourless solid (42 mg, 24% yield).

¹H NMR (CDCl₃) δ: 8.50 (s, 1H), 7.81 (m, 1H), 7.68 (dd, J=9.4, 5.6 Hz,1H), 7.51 (m, 3H), 7.19 (m, 1H), 6.63 (dd, J=9.4, 5.0 Hz, 1H), 4.76 (m,1H), 4.62 (d, J=7.9 Hz, 1H), 4.18 (m, 2H), 3.72 (m, 1H), 3.43 (s, 2H),2.76 (m, 2H), 1.77 (m, 5H), 1.53 (d, J=6.4 Hz, 3H).

MS (ESI, m/z): 492.3 [M+H⁺].

Example 169(1R,2S)-2-methyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-oneand(1S,2R)-2-methyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations BT and BL and usingprocedure E, a mixture of the title compounds was obtained as acolourless solid (43 mg, 24% yield).

¹H NMR (CDCl₃) δ: 8.10 (m, 1H), 7.86 (dd, J=8.8, 3.8 Hz, 1H), 7.71 (dd,J=9.4, 1.5 Hz, 1H), 7.55 (m, 3H), 7.22 (m, 1H), 6.67 (d, J=9.4 Hz, 1H),4.83 (m, 1H), 4.64 (m, 1H), 4.22 (m, 2H), 3.75 (dt, J=10.5, 7.3 Hz, 1H),3.46 (s, 2H), 2.79 (m, 2H), 1.87 (m, 5H), 1.57 (dd, J=6.4, 1.2 Hz, 3H).

MS (ESI, m/z): 492.4 [M+H⁺].

Example 170(1R,2R)-2-(1-hydroxy-1-methyl-ethyl)-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-oneand(1S,2S)-2-(1-hydroxy-1-methyl-ethyl)-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations BU and U and using procedureE, a mixture of the title compounds was obtained as a colourless foam(22 mg, 46% yield).

MS (ESI, m/z): 535.6 [M+H⁺].

Example 171(R)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from the compound of Example 132 and proceeding in analogy toExample 160, the title compound was obtained as a colourless foam (36%yield).

MS (ESI, m/z): 499.4 [M+H⁺].

Example 172N—((RS)-9-fluoro-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-N-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-acetamideand(RS)-1-{3-[(R)-3-(4-acetyl-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-2-oxo-oxazolidin-5-yl]-propylamino}-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

A solution of the compound of Example 13 (20 mg) and DIPEA (14 μL) wasreacted at 0° C. with Ac₂O (6 μL). The reaction mixture was furtherstirred at rt for 5 h. The solvent was removed under reduced pressureand the residue was dissolved in DCM and sequentially washed with waterand brine. The org. layer was dried over MgSO₄. The solvent was removedunder reduced pressure and the residue was purified by CC(DCM/MeOH/NH₄OH; 1000:50:4), affording a 1:1-mixture of the two possibleN-acetates as an off-white foam (18 mg; 83% yield).

MS (ESI, m/z): 537.5 [M+H⁺].

Example 173(S)-4-hydroxy-4-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one

To a solution of the compound of Preparation BD (75 mg) in EtOH (3 mL)were added the compound of Preparation AP (89 mg, 1.5 eq.) and K₂CO₃ (65mg, 3 eq.). The mixture was stirred at rt for 3 days. The solvent wasremoved under reduced pressure and the residue was partitioned betweenwater and DCM-MeOH (9:1). The phases were separated and the aq. layerwas extracted two more times with DCM-MeOH (9:1). The combined org.layers were dried over MgSO₄ and concentrated. The residue was purifiedby CC (DCM/MeOH/NH₄OH 1000:100:8) to afford the title compound as ayellow solid (26 mg, 26% yield).

MS (ESI, m/z): 494.2 [M+H⁺].

Example 174(RS)-9-fluoro-1-hydroxy-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from9-fluoro-1-hydroxy-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl]methyl4-methylbenzenesulfonate (prepared according to EP 1980251) and thecompound of Preparation AP and using procedure C, the title compound wasobtained as a yellow solid (85 mg, 65% yield).

MS (ESI, m/z): 511.2 [M+H⁺].

Example 175(RS)-1-({[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations AE and BW and usingprocedure C, the title compound was obtained as a beige solid (70 mg;20% yield).

MS (ESI, m/z): 464.4 [M+H⁺].

Example 176(RS)-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations AE and BX and usingprocedure C, the title compound was obtained as a colourless solid (130mg; 36% yield).

MS (ESI, m/z): 478.2 [M+H⁺].

Example 177(RS)-9-chloro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations BY and BK and usingprocedure E, the title compound was obtained as a pale yellow solid (31mg; 58% yield).

¹H NMR (CDCl₃) δ: 8.33 (m, 1H), 7.84 (dd, J=8.8, 4.4 Hz, 1H), 7.66 (dd,J=9.4, 3.5 Hz, 1H), 7.57 (dd, J=8.5, 2.3 Hz, 1H), 7.41 (dd, J=8.2, 1.8Hz, 1H), 7.11 (dd, J=8.5, 1.5 Hz, 1H), 6.66 (dd, J=9.4, 3.8 Hz, 1H),4.91 (m, 1H), 4.62 (m, 1H), 4.45 (m, 1H), 4.25 (m, 2H), 3.75 (m, 1H),3.45 (s, 2H), 2.61 (m, 2H), 1.78 (m, 5H).

MS (ESI, m/z): 512.3 [M+H⁺].

Example 178(RS)-9-chloro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations BY and U and using procedureE, the title compound was obtained as a colourless solid (14 mg; 26%yield).

¹H NMR (CDCl₃) δ: 8.73 (s, 1H), 7.68 (d, J=9.7 Hz, 1H), 7.39 (m, 2H),7.25 (m, 1H), 7.12 (d, J=8.2 Hz, 1H), 6.98 (m, 1H), 6.68 (d, J=9.4 Hz,1H), 4.91 (dd, J=8.2, 3.5 Hz, 1H), 4.65 (m, 1H), 4.46 (m, 1H), 4.30 (dd,J=13.2, 3.2 Hz, 1H), 4.06 (m, 1H), 3.61 (m, 1H), 3.39 (s, 2H), 2.64 (m,2H), 1.86 (m, 5H).

MS (ESI, m/z): 511.3 [M+H⁺].

Example 179(RS)-9-ethyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations BZ and U and using procedureE, the title compound was obtained as a colourless solid (11 mg; 36%yield).

¹H NMR (CDCl₃) δ: 8.56 (m, 1H), 7.68 (d, J=9.4 Hz, 1H), 7.39 (m, 2H),7.26 (m, 1H), 7.01 (m, 2H), 6.64 (d, J=9.4 Hz, 1H), 4.82 (t, J=5.3 Hz,1H), 4.65 (m, 1H), 4.37 (d, J=5.3 Hz, 2H), 4.06 (m, 1H), 3.61 (dd,J=8.5, 7.0 Hz, 1H), 3.39 (s, 2H), 2.80 (m, 4H), 1.71 (m, 5H), 1.29 (m,3H).

MS (ESI, m/z): 505.5 [M+H⁺].

Example 180(RS)-9-ethynyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations CA and U and using procedureE, the title compound was obtained as a colourless solid (10 mg; 21%yield).

MS (ESI, m/z): 501.2 [M+H⁺].

Example 181(1R*,2R*)-9-fluoro-4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylicacid methyl ester

Starting from the compounds of Preparations CB and U and using procedureE, the title compound was obtained as an off-white foam (23 mg; 20%yield).

MS (ESI, m/z): 553.6 [M+H⁺].

Example 182(1R*,2R*)-9-fluoro-2-hydroxymethyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations CC and U and using procedureE, the title compound was obtained as a white foam (44 mg; 38% yield).

MS (ESI, m/z): 525.3 [M+H⁺].

Example 183(1R*,2S*)-9-fluoro-2-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations CD and U and using procedureE, the title compound was obtained as an off-white foam (12 mg; 10%yield).

MS (ESI, m/z): 509.3 [M+H⁺].

Example 184(1R*,2S*)-9-fluoro-2-methyl-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations CD and AU and usingprocedure E, the title compound was obtained as an off-white foam (21mg; 18% yield).

MS (ESI, m/z): 509.3 [M+H⁺].

Example 185(1R*,2S*)-9-fluoro-2-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations CD and BK and usingprocedure E, the title compound was obtained as an off-white foam (64mg; 55% yield).

MS (ESI, m/z): 510.3 [M+H⁺].

Example 186(1R*,2R*)-9-fluoro-4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-2-carboxylicacid hydrochloride

A solution of the compound of Example 181 (20 mg) in dioxane (1 mL) wastreated with aq. HCl (37%; 0.142 mL) and stirred at 50° C. for 3 h. Thesolution was concentrated under reduced pressure and the residue wassuspended in EA/MeOH (4:1), filtered, washed with TBME and dried in HV,affording a gray solid (6 mg; 29% yield).

MS (ESI, m/z): 539.2 [M+H⁺].

Example 187(RS)-9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one

A solution of the compound of Example 2 (60 mg) in MeOH/AcOH (1:1, 2 mL)was hydrogenated over Pd/C (133 mg) overnight. The catalyst was filteredoff and thoroughly washed with MeOH and MeOH/DCM. The filtrate wasconcentrated under reduced pressure. The residue was taken up in waterand 28% aq. NH₄OH, filtered, washed with water and TBME and dried underreduced pressure, affording an off-white foam (45 mg; 75% yield).

MS (ESI, m/z): 481.5 [M+H⁺].

Example 188(1R*,2S*)-2-aminomethyl-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one188.i. (1R*,2S*)-methanesulfonic acid9-fluoro-4-oxo-1-{3-[2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-2-ylmethylester

Starting from the compounds of Preparations CE and U and using procedureE, the title compound was obtained as an off-white foam (79 mg; 30%yield).

MS (ESI, m/z): 603.3 [M+H⁺].

188.ii.(1R*,2S*)-2-azidomethyl-9-fluoro-1-{3-[2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

NaN₃ (25 mg) was added to a solution of intermediate 188.i (77 mg) inDMF (1.5 mL) and the resulting mixture was stirred at 80° C. for 1 h.Water and EA were added and the phases separated. The aq. layer wasextracted once more with EA and the combined org. layers were washedwith water and brine, dried over MgSO₄ and concentrated. The residue waspurified by CC (DCM/MeOH/NH₄OH 1000:50:4), affording a light yellow foam(57 mg; 81% yield).

MS (ESI, m/z): 550.5 [M+H⁺].

188.iii.(1R*,2S*)-2-aminomethyl-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

A solution of intermediate 188.ii (57 mg) in THF (1.5 mL) was treatedwith PPh₃ (30 mg) and water (19 μL). The mixture was heated at 70° C.overnight, concentrated under reduced pressure and the residue was takenin DCM. The DCM layer was extracted with 1M HCl and the aq. layer wasbasified with NH₄OH. The aq. layer was extracted with DCM/MeOH (9:1) andthe combined org. layers were dried over MgSO₄, concentrated andpurified by CC (DCM/MeOH/NH₄OH 1000:100:8), affording a light yellowfoam (26 mg; 48% yield).

MS (ESI, m/z): 524.3 [M+H⁺].

Example 189(S)-9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations CF and BJ and usingprocedure E, the title compound was obtained as an off-white foam (52mg; 32% yield).

MS (ESI, m/z): 480.5 [M+H⁺].

Example 190(S)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations CF and AR and usingprocedure E, the title compound was obtained as an off-white foam (64mg; 34% yield).

MS (ESI, m/z): 480.5 [M+H⁺].

Example 191(S)-9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations CF and BL and usingprocedure E, the title compound was obtained as an off-white foam (53mg; 27% yield).

MS (ESI, m/z): 496.1 [M+H⁺].

Example 192(S)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations CF and BK and usingprocedure E, the title compound was obtained as an off-white solid (73mg; 38% yield).

MS (ESI, m/z): 496.6 [M+H⁺].

Example 193(R)-9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations CG and BJ and usingprocedure E, the title compound was obtained as an off-white foam (56mg; 34% yield).

MS (ESI, m/z): 480.6 [M+H⁺].

Example 194(R)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations CG and AR and usingprocedure E, the title compound was obtained as an off-white foam (71mg; 38% yield).

MS (ESI, m/z): 480.6 [M+H⁺].

Example 195(R)-9-fluoro-1-{3-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations CG and BL and usingprocedure E, the title compound was obtained as a light yellow solid (52mg; 27% yield).

MS (ESI, m/z): 496.5 [M+H⁺].

Example 196(R)-9-fluoro-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations CG and BK and usingprocedure E, the title compound was obtained as a light yellow solid (55mg; 28% yield).

MS (ESI, m/z): 496.6 [M+H⁺].

Example 197(RS)-9-fluoro-1-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations A and CH and using procedureC, the title compound was obtained as a pale yellow solid (40 mg; 22%yield).

MS (ESI, m/z): 496.6 [M+H⁺].

Example 198(RS)-9-fluoro-1-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one

Starting from the compounds of Preparations A and BX and using procedureC, the title compound was obtained as a pale yellow solid (10 mg; 11%yield).

MS (ESI, m/z): 496.4 [M+H⁺].

Example 199(RS)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one

Starting from the compounds of Preparations CI and BK and usingprocedure E, the title compound was obtained as a light yellow solid(650 mg; 26% yield).

MS (ESI, m/z): 497.5 [M+H⁺].

Example 200(RS)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-one

A solution of the compound of Preparation CI (0.2 g, 0.975 mmol) and thecompound of Preparation BK (0.3 g, 0.975 mmol) in DCE/MeOH (1:1, 8 mL)was stirred at rt overnight. NaBH₄ (110 mg) was added and the mixturestirred at rt for 1 h. The mixture was quenched with HCl 1M andpartitioned between DCM and diluted NH₄OH. The org. phase was dried overMgSO₄ and concentrated. The residue was purified by CC (DCM/MeOH 19:1containing 1% NH₄OH). The title compound was obtained as a light rosefoam (78 mg; 16% yield).

MS (ESI, m/z): 499.5 [M+H⁺].

Example 201(RS)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1-methyl-1,2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-onedihydrochloride 201.i.((RS)-7-fluoro-3-oxo-5,6-dihydro-3H-pyrrolo[1,2,3-de]quinoxalin-6-yl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-carbamicacid tert-butyl ester

A suspension of the compound of Example 199 (0.6 g, 1.2 mmol) in DCM (10mL), MeOH (2 mL) and THF (5 mL) was treated with Boc₂O (526 mg, 2 eq.)was heated at reflux overnight. The volatiles were removed under reducedpressure and the residue purified by CC (EA) to give the desiredintermediate as a beige foam (0.61 g, 85% yield).

MS (ESI, m/z): 597.7 [M+H⁺].

201.ii.((RS)-7-fluoro-3-oxo-2,3,5,6-tetrahydro-1H-pyrrolo[1,2,3-de]quinoxalin-6-yl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-carbamicacid tert-butyl ester

A solution of intermediate 201.i (610 mg) in MeOH/DCM (4:1; 20 mL) wastreated with NaBH₄ (77 mg, 2 eq.) and stirred at rt for 2 h. The mixturewas quenched with HCl 1M and partitioned between DCM and diluted NH₄OH.The org. phase was dried over MgSO₄ and concentrated. The residue waspurified by CC (EA). The title compound was obtained as a beige foam(410 mg; 67% yield).

MS (ESI, m/z): 599.6 [M+H⁺].

201. iii.((R)-7-fluoro-1-methyl-3-oxo-2,3,5,6-tetrahydro-1H-pyrrolo[1,2,3-de]quinoxalin-6-yl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-carbamicacid tert-butyl ester

A solution of intermediate 201.ii (100 mg) in MeOH (3 mL) was treatedwith AcOH (0.019 mL), aq. formaldehyde (37%, 0.026 mL) and NaCNBH₃ (30mg). The mixture was stirred at rt for 3 h. The mixture was diluted withEA and water and the org. phase was washed with NaHCO₃ and brine, driedover MgSO₄ and concentrated. The residue was crystallized from ether togive the desired intermediate as a colourless solid (0.075 g, 73%yield).

MS (ESI, m/z): 613.7 [M+H⁺].

201. iv.(RS)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1-methyl-1,2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-onedihydrochloride

A suspension of intermediate 201.iii (0.068 g, 0.1 mmol) in HCl (4M indioxane, 1 mL) was stirred at rt for 15 min. The volatiles were removedunder reduced pressure and the solid was washed with ether and dried atHV. The title salt was isolated as a grey solid (0.068 g; quant.).

MS (ESI, m/z): 513.6 [M+H⁺].

Example 202(RS)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1-(3-hydroxypropyl)-1,2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-onedihydrochloride 202.i.((R)-7-fluoro-1-(3-hydroxypropyl)-methyl-3-oxo-2,3,5,6-tetrahydro-1H-pyrrolo[1,2,3-de]quinoxalin-6-yl)-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-carbamicacid tert-butyl ester

A solution of intermediate 201.ii (100 mg) in MeOH (3 mL) was treatedwith AcOH (0.019 mL), aq. formaldehyde (37%, 0.026 mL) and3-[(tert-butyldimethylsilyl)oxy]-1-propanal (88 mg, commercial). Themixture was stirred at rt for 5 h. The mixture was diluted with EA andwater and the org. phase was washed with NaHCO₃ and brine, dried overMgSO₄ and concentrated. The residue was purified by CC (EA) to give thedesired intermediate as a yellowish oil (0.11 g, 62% yield).

MS (ESI, m/z): 771.6 [M+H⁺].

202. ii.(RS)-7-fluoro-6-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1-(3-hydroxypropyl)-1,2,5,6-tetrahydro-pyrrolo[1,2,3-de]quinoxalin-3-onedihydrochloride

A suspension of intermediate 202.i (0.11 g, 0.14 mmol) in HCl (4M indioxane, 1.5 mL) was stirred at rt for 15 min. The volatiles wereremoved under reduced pressure and the solid was washed with ether anddried at HV. The title salt was isolated as a grey solid (0.071 g; 78%yield).

MS (ESI, m/z): 557.3 [M+H⁺].

Pharmacological Properties of the Invention Compounds

In Vitro Assays

Experimental Methods:

Minimal inhibitory concentrations (MICs; mg/l) were determined incation-adjusted Mueller-Hinton Broth by a microdilution method followingthe description given in “Methods for Dilution AntimicrobialSusceptibility Tests for Bacteria that Grow Aerobically”, Approvedstandard, 7^(th) ed., Clinical and Laboratory Standards Institute (CLSI)Document M7-A7, Wayne, Pa., USA, 2006.

Results:

All Example compounds were tested against several Gram positive and Gramnegative bacteria such as S. aureus, E. faecalis, S. pneumoniae, M.catarrhalis, A. baumanii, E. coli or P. aeruginosa.

Typical antibacterial test results are given in the table hereafter (MICin mg/l).

Example MIC for MIC for No. M. catarrhalis A894 Example No. M.catarrhalis A894 1 ≦0.031 2 ≦0.031 3 ≦0.031 4 ≦0.031 5 ≦0.031 6 0.125 7≦0.031 8 ≦0.031 9 ≦0.031 10 ≦0.031 11 0.063 12 ≦0.031 13 ≦0.031 14≦0.031 15 ≦0.031 16 ≦0.031 17 ≦0.031 18 ≦0.031 19 ≦0.031 20 ≦0.031 21≦0.031 22 ≦0.031 23 ≦0.031 24 ≦0.031 25 ≦0.031 26 0.25 27 0.5 28 ≦0.03129 ≦0.031 30 0.031 31 16 32 0.031 33 16 34 ≦0.031 35 ≦0.031 36 8 37 1 3816 39 ≦0.031 40 0.125 41 0.5 42 2 43 1 44 0.125 45 0.063 46 ≦0.031 47≦0.031 48 ≦0.031 49 ≦0.031 50 ≦0.031 51 ≦0.031 52 ≦0.031 53 ≦0.031 540.25 55 ≦0.031 56 ≦0.031 57 ≦0.031 58 ≦0.031 59 4 60 ≦0.031 61 ≦0.031 62≦0.031 63 0.031 64 ≦0.031 65 ≦0.031 66 ≦0.031 67 ≦0.063 68 ≦0.031 69≦0.031 70 ≦0.031 71 ≦0.031 72 ≦0.031 73 ≦0.031 74 ≦0.031 75 ≦0.031 76≦0.031 77 0.031 78 ≦0.031 79 ≦0.031 80 ≦0.031 81 ≦0.031 82 0.25 83≦0.031 84 0.063 85 ≦0.031 86 ≦0.031 87 ≦0.031 88 ≦0.031 89 0.063 90≦0.031 91 ≦0.031 92 ≦0.031 93 ≦0.031 94 ≦0.031 95 ≦0.031 96 ≦0.031 97≦0.031 98 0.25 99 ≦0.031 100 0.031 101 ≦0.031 102 ≦0.031 103 ≦0.031 104≦0.031 105 ≦0.031 106 ≦0.031 107 8 108 ≦0.031 109 ≦0.031 110 ≦0.031 1110.125 112 ≦0.031 113 ≦0.031 114 ≦0.031 115 ≦0.031 116 ≦0.031 117 13.031118 13.031 119 ≦0.031 120 0.125 121 0.125 122 0.5 123 0.125 124 ≦0.031125 ≦0.031 126 ≦0.031 127 ≦0.031 128 ≦0.031 129 ≦0.031 130 ≦0.031 131≦0.031 132 ≦0.031 133 ≦0.031 134 ≦0.031 135 ≦0.031 136 ≦0.031 137 ≦0.031138 ≦0.031 139 ≦0.031 140 ≦0.031 141 ≦0.031 142 ≦0.031 143 ≦0.031 144≦0.031 145 ≦0.031 146 ≦0.031 147 ≦0.031 148 ≦0.031 149 ≦0.031 150 ≦0.031151 ≦0.031 152 ≦0.031 153 ≦0.031 154 ≦0.031 155 ≦0.031 156 ≦0.031 157 2158 ≦0.031 159 ≦0.031 160 ≦0.031 161 0.125 162 0.25 163 0.031 164 0.031165 0.125 166 ≦0.031 167 ≦0.031 168 ≦0.031 169 ≦0.031 170 0.25 171≦0.031 172 0.25 173 0.125 174 ≦0.031 175 ≦0.031 176 ≦0.031 177 ≦0.031178 ≦0.031 179 ≦0.031 180 ≦0.031 181 ≦0.031 182 ≦0.031 183 ≦0.031 184≦0.031 185 ≦0.031 186 0.5 187 ≦0.031 188 ≦0.031 189 ≦0.031 190 ≦0.031191 ≦0.031 192 ≦0.031 193 ≦0.031 194 ≦0.031 195 ≦0.031 196 ≦0.031 197≦0.031 198 ≦0.031 199 ≦0.031 200 ≦0.031 201 ≦0.031 202 0.063

The invention claimed is:
 1. A compound of formula I

wherein “-----” is a bond or is absent; R⁰ represents H or, in the case“-----” is a bond, may also represent (C₁-C₃)alkoxy; R¹ representscyano, (C₁-C₃)alkyl, or ethynyl; U represents CH or N when “-----” is abond, or, in case “----” is absent, U represents CH₂, NH or NR⁹; Vrepresents CH, CR⁶, or N; R² represents H, (C₁-C₃)alkylcarbonyl or agroup of the formula —CH₂—R³; R³ represents H, (C₁-C₃)alkyl or(C₁-C₃)hydroxyalkyl; R⁴ represents H or, in the cases wherein n is not 0and R⁵ is H, may also represent OH; R⁵ represents H, (C₁-C₃)alkyl,(C₁-C₃)hydroxyalkyl, (C₁-C₃)aminoalkyl, (C₁-C₃)alkoxy(C₁-C₃)alkyl,carboxy or (C₁-C₃)alkoxycarbonyl; R⁶ represents (C₁-C₃)hydroxyalkyl,carboxy, (C₁-C₃)alkoxycarbonyl, or a group —(CH₂)_(q)—NR⁷R⁸ wherein q is1, 2, or 3 and each of R⁷ and R⁸ independently represents H or(C₁-C₃)alkyl or R⁷ and R⁸ form together with a nitrogen atom bearingthem a pyrrolidinyl, piperidinyl, morpholinyl or thiomorpholinyl ring;R⁹ represents (C₁-C₃)alkyl, 2-hydroxy-ethyl, 2-hydroxy-propyl or3-hydroxy-propyl; A represents —(CH₂)_(p)—, —CH₂CH₂CH(OH)— or—COCH₂CH(OH)—; G represents a phenyl group which is substituted once ortwice in the meta and/or para position(s) by substituents selectedindependently from (C₁-C₄)alkyl, (C₁-C₃)alkoxy, or a halogen, or G isone of the formulae G¹ and G² below

wherein Q is 0 or S and X is CH or N; and Y¹, Y² and Y³ each representCH, or Y¹ and Y³ each represent CH and Y² represents N, or Y¹ representsN, Y² represents CH or N and Y³ represents CH, or Y¹ and Y² eachrepresent CH and Y³ represents N; and n is 0 when A represents—CH₂CH₂CH(OH)— or —COCH₂CH(OH)—, and n is 0, 1, or 2 when A represents(CH₂)_(p), p being 1, 2, 3 or 4, with the proviso that the sum of n andp is then 2, 3, or 4; or a salt of such a compound.
 2. The compoundaccording to claim 1, wherein R¹ represents cyano or (C₁-C₃)alkyl; Urepresents CH or N when “-----” is a bond, or, in case “----” is absent,U represents CH₂ or NH; R⁵ represents H, (C₁-C₃)alkyl,(C₁-C₃)hydroxyalkyl, (C₁-C₃)alkoxy(C₁-C₃)alkyl or (C₁-C₃)alkoxycarbonyl;or a salt thereof of such a compound.
 3. The compound according to claim1, wherein “-----” is a bond, V represents CH and U represents CH or N,or V represents CR⁶ and U represents CH, or V represents N and Urepresents CH; or “-----” is absent, V represents CH and U representsCH₂, NH or NR⁹; R² represents H, acetyl or a group of the formula—CH₂—R³; R⁶ represents (C₁-C₃)hydroxyalkyl, carboxy,(C₁-C₃)alkoxycarbonyl or a group —(CH₂)_(q)—NR⁷R⁸ wherein q is 1, 2 or 3and each of R⁷ and R⁸ independently represents H or (C₁-C₃)alkyl or R⁷and R⁸ form together with the nitrogen atom bearing them a pyrrolidinylor piperidinyl ring; and each of Y¹ and Y³ represents CH, or one of Y¹and Y³ represents N and the other represents CH; or a salt thereof. 4.The compound according to claim 1, wherein R¹ represents (C₁-C₃)alkyl;or a salt thereof.
 5. The compound according to claim 1, wherein Vrepresents CH; or a salt thereof.
 6. The compound according to claim 1,wherein V represents N; or a salt thereof.
 7. The compound according toclaim 1, wherein “-----” is a bond and U represents CH or N; or a saltthereof.
 8. The compound according to claim 1, wherein “-----” is absentand U represents CH₂, NH or NR⁹; or a salt thereof.
 9. The compoundaccording to claim 1, wherein G is a group of the formula

wherein Q represents 0 or S; or a salt thereof.
 10. The compoundaccording to claim 1, wherein said compound is:4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-9-carbonitrile;4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-9-carbonitrile;9-methyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;9-ethyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;or9-ethynyl-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;or a salt thereof.
 11. A pharmaceutical composition comprising atherapeutically effective amount of a compound according to claim 1, ora pharmaceutically acceptable salt thereof, and at least onetherapeutically inert excipient.
 12. A method of treating a bacterialinfection in a subject comprising administering to said subject apharmaceutically active amount of the compound according to claim 1, ora pharmaceutically acceptable salt thereof.
 13. The compound accordingto claim 1, wherein R¹ represents ethynyl; or a salt thereof.